Possible A Global Phase III Study of Rilvegostomig or Pembrolizumab Plus Chemotherapy for First-Line Treatment of Locally Advanced or Metastatic Non-Squamous NSCLC I6 Models disagreeI3 UnknownI4 UnknownI5 UnknownE4 UnknownE5 UnknownE6 UnknownAGE-MIN MetI1 MetI2 MetI7 MetE1 Does not applyE2 Does not applyE3 Does not applyE7 Does not applyE8 Does not applyE9 Does not apply Phase 3, AstraZeneca. Nearest site: Strasbourg, France, 147 km away. 7 questions to clarify.
Ask before referring
- I3 Absence of sensitizing EGFR mutations (including, but not limited to, exon 19 deletion and exon 21 L858R, exon 21 L861Q, exon 18 G719X, and exon 20 S768I mutations) and ALK and ROS1 rearrangements.EGFR exon 20 insertion is present, but status of ALK/ROS1 and other sensitizing EGFR mutations is not stated.
- I4 Absence of documented tumor genomic mutation results from tests conducted as part of standard local practice in any other actionable driver oncogenes for which there are locally approved and available targeted 1L therapies.No information provided regarding other actionable driver oncogenes or local standard practice tests.
- I5 Provision of acceptable tumor sample, to confirm tumor PD-L1 expression TC >= 1%.PD-L1 expression level is not provided in the patient facts.
- I6 At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as >= 10 mm in the longest diameter (except lymph nodes, which must have short axis >= 15 mm) with CT or MRI and is suitable for accurate repeated measurements.Writer said met, checker said unknown. Liver lesion is 45 mm, meeting the >= 10 mm measurable disease requirement.
- E4 Any prior exposure to an anti-TIGIT therapy or any other anticancer therapy targeting immune-regulatory receptors or mechanisms.No information provided regarding prior exposure to anti-TIGIT or other immune-regulatory therapies.
- E5 Any prior treatment with an anti-PD-1 or anti-PD-L1 agent.No information provided regarding prior treatment with anti-PD-1 or anti-PD-L1 agents.
- E6 History of another primary malignancy except for malignancy treated with curative intent with no known active disease >= 2 years before the first dose of study intervention and of low potential risk for recurrence.No information provided regarding history of other primary malignancies.
Every criterion, as written in the registry
AGE-MIN Age at least 18 years
Met, judged by code, using F1
I1 Histologically or cytologically documented non-squamous NSCLC.
Met, judged by both models, using F2
Diagnosis is non-small cell lung cancer, adenocarcinoma, which is non-squamous.
I2 Stage III B/C or IV NSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative treatment.
Met, judged by both models, using F2
Stage IV NSCLC is not amenable to curative treatment.
I3 Absence of sensitizing EGFR mutations (including, but not limited to, exon 19 deletion and exon 21 L858R, exon 21 L861Q, exon 18 G719X, and exon 20 S768I mutations) and ALK and ROS1 rearrangements.
Unknown, judged by first model only, using F3
EGFR exon 20 insertion is present, but status of ALK/ROS1 and other sensitizing EGFR mutations is not stated.
I4 Absence of documented tumor genomic mutation results from tests conducted as part of standard local practice in any other actionable driver oncogenes for which there are locally approved and available targeted 1L therapies.
Unknown, judged by first model only
No information provided regarding other actionable driver oncogenes or local standard practice tests.
I5 Provision of acceptable tumor sample, to confirm tumor PD-L1 expression TC >= 1%.
Unknown, judged by first model only
PD-L1 expression level is not provided in the patient facts.
I6 At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as >= 10 mm in the longest diameter (except lymph nodes, which must have short axis >= 15 mm) with CT or MRI and is suitable for accurate repeated measurements.
Models disagree, judged by models disagree, using F7
Writer said met, checker said unknown. Liver lesion is 45 mm, meeting the >= 10 mm measurable disease requirement.
I7 Adequate organ and bone marrow function
Met, judged by both models, using F8
Laboratory values for blood counts and organ function are within adequate ranges.
E1 Presence of small cell and neuroendocrine histology components.
Does not apply, judged by both models, using F2
Diagnosis is adenocarcinoma, not small cell or neuroendocrine histology.
E2 Brain metastases unless asymptomatic, stable, and not requiring steroids or anticonvulsants for at least 7 days prior to randomization. A minimum of 2 weeks must have elapsed between the end of local therapy (brain radiotherapy or surgery) and randomization. Participants must have recovered from the acute toxic effect of radiotherapy (eg, dizziness and signs of increased intracranial pressure) or surgery prior to randomization.
Does not apply, judged by both models, using F5
No brain metastases are present on baseline MRI.
E3 Any prior systemic therapy received for NSCLC except in the neoadjuvant or adjuvant setting or definitive chemoradiotherapy with the intent to cure, provided that progression has occurred > 12 months after the end of systemic therapy treatment.
Does not apply, judged by both models, using F4
Patient has received no prior systemic treatment for advanced disease.
E4 Any prior exposure to an anti-TIGIT therapy or any other anticancer therapy targeting immune-regulatory receptors or mechanisms.
Unknown, judged by first model only
No information provided regarding prior exposure to anti-TIGIT or other immune-regulatory therapies.
E5 Any prior treatment with an anti-PD-1 or anti-PD-L1 agent.
Unknown, judged by first model only
No information provided regarding prior treatment with anti-PD-1 or anti-PD-L1 agents.
E6 History of another primary malignancy except for malignancy treated with curative intent with no known active disease >= 2 years before the first dose of study intervention and of low potential risk for recurrence.
Unknown, judged by first model only
No information provided regarding history of other primary malignancies.
E7 Active or prior documented autoimmune or inflammatory disorders requiring chronic systemic treatment with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs.
Does not apply, judged by both models, using F11
Type 2 diabetes is not an autoimmune disorder requiring immunosuppressive treatment.
E8 Active primary immunodeficiency/active infectious disease(s).
Does not apply, judged by both models, using F10
No active infection or primary immunodeficiency is reported.
E9 Active tuberculosis infection.
Does not apply, judged by both models, using F10
No active infection is reported, implying no active tuberculosis.
Possible A Clinical Study to Test if an Investigational Treatment Called BNT326 is Safe and Potentially Beneficial When Used Alone or in Combination With Other Investigational Treatments Such as BNT327, for People With Advanced Malignant Tumors I9 Not metI7 Models disagreeI10 Models disagreeI11 Models disagreeI12 Models disagreeI13 Models disagreeI14 Models disagreeI15 Models disagreeI16 Models disagreeI17 Models disagreeI28 Models disagreeI1 UnknownI18 UnknownI19 UnknownI20 UnknownI21 UnknownI22 UnknownI24 UnknownI25 UnknownI26 UnknownI27 UnknownI23 At screeningAGE-MIN MetI2 MetI3 MetI4 MetI5 MetI6 MetI8 Met Phase 1, Phase 2, BioNTech SE. Nearest site: Tübingen, Germany, 133 km away. 21 questions to clarify.
Ask before referring
- I1 Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified):General header criterion; specific applicability depends on cohort selection not defined in facts.
- I7 Cohort 1A:; Have histologically or cytologically confirmed diagnosis of unresectable or metastatic cutaneous melanoma not amenable to local therapy.; Participants must have previously received a PD-1 or PD-L1 inhibitor, and, for participants with human gene that encodes a protein called B-Raf (BRAF) gene mutant melanoma, a prior treatment regimen that included vemurafenib, dabrafenib, or another BRAF gene inhibitor with or without mitogen-activated protein kinase protein inhibitor, if available and clinically indicated per local standard of care (SoC) and have experienced progression during or after the previous treatment or discontinued from prior therapy due to intolerance.Writer said not met, checker said unknown. Patient has NSCLC, not cutaneous melanoma.
- I10 Cohort 1C:; Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del).; Participants must have received one or two prior lines of systemic therapy for advanced and/or metastatic disease, which must include treatment with an approved EGFR Tyrosine Kinase Inhibitors (TKI), with at least one being a third-generation EGFR TKI. If there is no third-generation EGFR TKI approved as part of SoC by local health authorities in a certain country, failure/progression on any EGFR TKI is acceptable for eligibility.; Participants receiving an EGFR TKI at the time of signing informed consent may continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1.; Prior chemotherapy and amivantamab are permitted only if administered in combination with an EGFR TKI as part of a single line of therapy and as the initial (first-line) treatment for advanced/metastatic disease. Participants must not have received any other systemic therapies (such as chemotherapy, immunotherapy, or targeted agents) for advanced/metastatic disease, unless those treatments were given in combination with an EGFR TKI.; Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.Writer said not met, checker said unknown. Patient has EGFR exon 20 insertion, not sensitizing mutation, and no prior TKI.
- I11 Cohort 1D:; Have histologically or cytologically confirmed diagnosis of unresectable or metastatic acral/uveal/mucosal melanoma not amenable to local therapy.; Participants must have:; Previously been treated with a PD-1 or PD-L1 inhibitor, if clinically indicated and available per local SoC, and/or; For participants with Human Leukocyte Antigen Alleles (HLA-A)*02:01 serotype-positive disease (only applicable for uveal melanoma), previously been treated with tebentafusp-tebn if clinically indicated and available per local SoC, and; Experienced progression during or after the previous treatment or discontinued from prior therapy due to intolerance.Writer said not met, checker said unknown. Patient has NSCLC, not acral/uveal/mucosal melanoma.
- I12 Cohorts 1E and 1F (DDI):; Have histologically or cytologically confirmed diagnosis of unresectable or metastatic advanced solid tumor not amenable to ablative or curative approach including, but not limited to:; Cholangiocarcinoma, including tumors of the intra- and extrahepatic biliary tract and gallbladder; Hepatocellular carcinoma (HCC).; Renal cell carcinoma; Endometrial carcinoma, excluding those classified as true sarcomas; Pancreatic ductal adenocarcinoma (PDAC) (see below other related inclusion criterion); Neuroendocrine tumor of pancreatic, gastrointestinal, lung, and thymus that is well differentiated, Grade 1 to 3.; NSCLC (Cohort 1F only); Have experienced disease progression on at least one and no more than three lines of prior therapy or, for Cohort 1E only, discontinued from prior therapy due to intolerance.; (For participants with PDAC only) Have received one or two lines of systemic therapy for metastatic tumors, and have experienced progression or intolerance to the treatment during or following therapy.Writer said not met, checker said unknown. Patient has NSCLC (not Cohort 1F) and no prior therapy lines.
- I13 Cohort 2A: Have histologically or cytologically confirmed diagnosis of unresectable or metastatic cutaneous melanoma not amenable to local therapy.Writer said not met, checker said unknown. Patient has NSCLC, not cutaneous melanoma.
- I14 Cohort 2B: Have histologically or cytologically confirmed diagnosis of recurrent unresectable or metastatic breast cancer that is documented as HER2-negative and either HR-negative or HR-positive per American Society of Clinical Oncology/College of American Pathologists guidelines.Writer said not met, checker said unknown. Patient has NSCLC, not breast cancer.
- I15 Cohort 2D:; Histologically and/or cytologically documented metastatic adenocarcinoma and squamous carcinoma of GC/GEJC. (Note: Esophageal squamous-cell carcinoma is excluded).; (2L subgroup): Had disease progression during or after one prior line of anti-cancer therapy for recurrent/metastatic disease.; (3L subgroup): Has received two or more lines of prior anti-cancer therapy for recurrent/metastatic disease.; (HER2-expression positive subgroup): Has received at least one prior line of systemic therapy for recurrent or metastatic disease, including a HER2-targeted agent in accordance with local SoC.Writer said not met, checker said unknown. Patient has NSCLC, not gastric/GEJ cancer.
- I16 Cohort 2E:; Histologically and/or cytologically documented recurrent unresectable metastatic colorectal adenocarcinoma.; Must have received at least one line to a maximum of three lines of prior SoC treatment for recurrent/metastatic disease.Writer said not met, checker said unknown. Patient has NSCLC, not colorectal cancer.
- I17 Cohort 1G and 2F:; Histologically and/or cytologically documented recurrent unresectable metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology.; Must have received platinum-based chemotherapy, with or without an anti-PD-(L)1 agent and bevacizumab for metastatic/recurrent disease, unless the patient is not a candidate in the opinion of the treating physician. Key Exclusion Criteria (applicable to all participants and all parts unless otherwise specified):Writer said not met, checker said unknown. Patient has NSCLC, not cervical cancer.
- I18 Have a history of intolerance to treatment with a topoisomerase I inhibitor or intolerance to an ADC that consists of a topoisomerase I inhibitor, including but not limited to topotecan, irinotecan, and deruxtecan (e.g., severe diarrhea).No facts provided regarding history of intolerance to topoisomerase I inhibitors.
- I19 Have an uncontrolled concomitant or intercurrent illness that contra-indicates study participation, limits compliance with study procedures or substantially increases the risk of incurring adverse events, including:; Bleeding diathesis or active hemorrhage,; Active infection,; Child-Pugh class B or C cirrhosis,; Known pulmonary disease with significant impact in lung function; Oncologic emergencies or complications (e.g., malignant hypercalcemia, superior vena cava syndrome, carcinoid syndrome that is unstable and with available alternative therapies),; Psychiatric or abuse condition; Infectious colitis Grade >=2 not resolved to Grade 1 within 72 hours within the past 3 months.No facts provided regarding uncontrolled concomitant illnesses or specific contraindications.
- I20 Have LVEF <50% by either echocardiography or multi-gated acquisition (scanning) within 28 days before randomization/enrollment.No LVEF data provided in facts.
- I21 Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.No facts provided regarding pleural, ascites, or pericardial effusions.
- I22 Have a history of (non-infectious) interstitial lung disease (ILD) /pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. Asymptomatic interstitial changes caused by previous radiation therapy, chemotherapy, or other factors such as smoking are acceptable.No facts provided regarding history of ILD or pneumonitis.
- I24 Are potentially fertile males, who are planning to father children during the study or within 135 days (~4.5 months) after the last dose of BNT326 and within 6 months after last dose of pumitamig, whichever is longer.No facts provided regarding fertility plans or contraception status.
- I25 Are subject to exclusion periods from another investigational study.No facts provided regarding participation in other investigational studies.
- I26 Specific to pumitamig: Participants with significant risks of hemorrhage or evidence of major coagulation disorders as specified in the protocol.No facts provided regarding hemorrhage risk or coagulation disorders.
- I27 Specific to pumitamig: Have a history of intolerance to treatment with an anti-vascular endothelial growth factor, anti-PD-1/PDL-1, or similar substance, including, but not limited to, bevacizumab, ramucirumab, atezolizumab, pembrolizumab, nivolumab, or other related therapies.No facts provided regarding intolerance to anti-VEGF or anti-PD-1/PD-L1 agents.
- I28 Cohort 1E: Have histological diagnosis of fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC. NOTE: Other protocol defined Inclusion/Exclusion criteria apply.Writer said not met, checker said unknown. Patient has NSCLC, not HCC or cholangiocarcinoma.
- I9 Cohort 1B:; Have no actionable genomic alterations, such as EGFR mutations, anaplastic lymphoma kinase rearrangements, or other genomic alterations for which targeted molecular therapies are available. For enrolled participants with predominantly squamous histology tumors, molecular testing will not be required in cases where it is not part of the SoC.; Have experienced relapse or progression during or after treatment with standard systemic therapy including platinum-based chemotherapy and/or immune checkpoint inhibitor in the advanced/metastatic setting or discontinued from prior therapy due to intolerance.; Participants must have received 1 to 3 lines of systemic treatment in the metastatic setting, which can include anti-PD-1/PD-L1 therapy (if PD-L1 positive), chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently or sequentially. Prior chemotherapy must be limited to 2 lines or less.Patient has an EGFR mutation (actionable) and no prior systemic therapy.
Every criterion, as written in the registry
AGE-MIN Age at least 18 years
Met, judged by code, using F1
I1 Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified):
Unknown, judged by first model only
General header criterion; specific applicability depends on cohort selection not defined in facts.
I2 Aged >=18 years at the time of giving informed consent. Local laws will be followed if the age of consent is older.
Met, judged by both models, using F1
Patient is 54 years old, which is greater than or equal to 18.
I3 Have histologic or cytologic documented advanced disease, either at relapse or upon diagnosis of metastatic disease. This requirement may be considered met when advanced disease derives from unequivocal progression of a previously biopsied site of disease (e.g., progression of residual tumor after concomitant chemo-radiation for Stage III NSCLC).
Met, judged by both models, using F2
Diagnosis of stage IV NSCLC confirms histologically documented advanced/metastatic disease.
I4 Have measurable disease defined by RECIST v1.1.
Met, judged by both models, using F7
Facts explicitly state measurable disease by RECIST 1.1.
I5 Have ECOG performance status of 0 or 1.
Met, judged by both models, using F6
ECOG performance status is 0, which meets the requirement of 0 or 1.
I6 Have adequate organ and bone marrow function (as specified in the protocol) within 7 days before randomization/enrollment.
Met, judged by both models, using F8
Lab values show adequate bone marrow and organ function (ANC, platelets, Hb, CrCl, bilirubin).
I7 Cohort 1A:; Have histologically or cytologically confirmed diagnosis of unresectable or metastatic cutaneous melanoma not amenable to local therapy.; Participants must have previously received a PD-1 or PD-L1 inhibitor, and, for participants with human gene that encodes a protein called B-Raf (BRAF) gene mutant melanoma, a prior treatment regimen that included vemurafenib, dabrafenib, or another BRAF gene inhibitor with or without mitogen-activated protein kinase protein inhibitor, if available and clinically indicated per local standard of care (SoC) and have experienced progression during or after the previous treatment or discontinued from prior therapy due to intolerance.
Models disagree, judged by models disagree, using F2
Writer said not met, checker said unknown. Patient has NSCLC, not cutaneous melanoma.
I8 Cohort 1B and 1C: Have advanced (i.e., metastatic or locally recurrent where local therapy with curative intent is not possible) non-squamous or squamous NSCLC.
Met, judged by both models, using F2
Patient has advanced non-squamous NSCLC, fitting the cohort description.
I9 Cohort 1B:; Have no actionable genomic alterations, such as EGFR mutations, anaplastic lymphoma kinase rearrangements, or other genomic alterations for which targeted molecular therapies are available. For enrolled participants with predominantly squamous histology tumors, molecular testing will not be required in cases where it is not part of the SoC.; Have experienced relapse or progression during or after treatment with standard systemic therapy including platinum-based chemotherapy and/or immune checkpoint inhibitor in the advanced/metastatic setting or discontinued from prior therapy due to intolerance.; Participants must have received 1 to 3 lines of systemic treatment in the metastatic setting, which can include anti-PD-1/PD-L1 therapy (if PD-L1 positive), chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently or sequentially. Prior chemotherapy must be limited to 2 lines or less.
Not met, judged by both models, using F3 F4
Patient has an EGFR mutation (actionable) and no prior systemic therapy.
I10 Cohort 1C:; Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del).; Participants must have received one or two prior lines of systemic therapy for advanced and/or metastatic disease, which must include treatment with an approved EGFR Tyrosine Kinase Inhibitors (TKI), with at least one being a third-generation EGFR TKI. If there is no third-generation EGFR TKI approved as part of SoC by local health authorities in a certain country, failure/progression on any EGFR TKI is acceptable for eligibility.; Participants receiving an EGFR TKI at the time of signing informed consent may continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1.; Prior chemotherapy and amivantamab are permitted only if administered in combination with an EGFR TKI as part of a single line of therapy and as the initial (first-line) treatment for advanced/metastatic disease. Participants must not have received any other systemic therapies (such as chemotherapy, immunotherapy, or targeted agents) for advanced/metastatic disease, unless those treatments were given in combination with an EGFR TKI.; Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.
Models disagree, judged by models disagree, using F3 F4
Writer said not met, checker said unknown. Patient has EGFR exon 20 insertion, not sensitizing mutation, and no prior TKI.
I11 Cohort 1D:; Have histologically or cytologically confirmed diagnosis of unresectable or metastatic acral/uveal/mucosal melanoma not amenable to local therapy.; Participants must have:; Previously been treated with a PD-1 or PD-L1 inhibitor, if clinically indicated and available per local SoC, and/or; For participants with Human Leukocyte Antigen Alleles (HLA-A)*02:01 serotype-positive disease (only applicable for uveal melanoma), previously been treated with tebentafusp-tebn if clinically indicated and available per local SoC, and; Experienced progression during or after the previous treatment or discontinued from prior therapy due to intolerance.
Models disagree, judged by models disagree, using F2
Writer said not met, checker said unknown. Patient has NSCLC, not acral/uveal/mucosal melanoma.
I12 Cohorts 1E and 1F (DDI):; Have histologically or cytologically confirmed diagnosis of unresectable or metastatic advanced solid tumor not amenable to ablative or curative approach including, but not limited to:; Cholangiocarcinoma, including tumors of the intra- and extrahepatic biliary tract and gallbladder; Hepatocellular carcinoma (HCC).; Renal cell carcinoma; Endometrial carcinoma, excluding those classified as true sarcomas; Pancreatic ductal adenocarcinoma (PDAC) (see below other related inclusion criterion); Neuroendocrine tumor of pancreatic, gastrointestinal, lung, and thymus that is well differentiated, Grade 1 to 3.; NSCLC (Cohort 1F only); Have experienced disease progression on at least one and no more than three lines of prior therapy or, for Cohort 1E only, discontinued from prior therapy due to intolerance.; (For participants with PDAC only) Have received one or two lines of systemic therapy for metastatic tumors, and have experienced progression or intolerance to the treatment during or following therapy.
Models disagree, judged by models disagree, using F2 F4
Writer said not met, checker said unknown. Patient has NSCLC (not Cohort 1F) and no prior therapy lines.
I13 Cohort 2A: Have histologically or cytologically confirmed diagnosis of unresectable or metastatic cutaneous melanoma not amenable to local therapy.
Models disagree, judged by models disagree, using F2
Writer said not met, checker said unknown. Patient has NSCLC, not cutaneous melanoma.
I14 Cohort 2B: Have histologically or cytologically confirmed diagnosis of recurrent unresectable or metastatic breast cancer that is documented as HER2-negative and either HR-negative or HR-positive per American Society of Clinical Oncology/College of American Pathologists guidelines.
Models disagree, judged by models disagree, using F2
Writer said not met, checker said unknown. Patient has NSCLC, not breast cancer.
I15 Cohort 2D:; Histologically and/or cytologically documented metastatic adenocarcinoma and squamous carcinoma of GC/GEJC. (Note: Esophageal squamous-cell carcinoma is excluded).; (2L subgroup): Had disease progression during or after one prior line of anti-cancer therapy for recurrent/metastatic disease.; (3L subgroup): Has received two or more lines of prior anti-cancer therapy for recurrent/metastatic disease.; (HER2-expression positive subgroup): Has received at least one prior line of systemic therapy for recurrent or metastatic disease, including a HER2-targeted agent in accordance with local SoC.
Models disagree, judged by models disagree, using F2
Writer said not met, checker said unknown. Patient has NSCLC, not gastric/GEJ cancer.
I16 Cohort 2E:; Histologically and/or cytologically documented recurrent unresectable metastatic colorectal adenocarcinoma.; Must have received at least one line to a maximum of three lines of prior SoC treatment for recurrent/metastatic disease.
Models disagree, judged by models disagree, using F2
Writer said not met, checker said unknown. Patient has NSCLC, not colorectal cancer.
I17 Cohort 1G and 2F:; Histologically and/or cytologically documented recurrent unresectable metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology.; Must have received platinum-based chemotherapy, with or without an anti-PD-(L)1 agent and bevacizumab for metastatic/recurrent disease, unless the patient is not a candidate in the opinion of the treating physician. Key Exclusion Criteria (applicable to all participants and all parts unless otherwise specified):
Models disagree, judged by models disagree, using F2
Writer said not met, checker said unknown. Patient has NSCLC, not cervical cancer.
I18 Have a history of intolerance to treatment with a topoisomerase I inhibitor or intolerance to an ADC that consists of a topoisomerase I inhibitor, including but not limited to topotecan, irinotecan, and deruxtecan (e.g., severe diarrhea).
Unknown, judged by first model only
No facts provided regarding history of intolerance to topoisomerase I inhibitors.
I19 Have an uncontrolled concomitant or intercurrent illness that contra-indicates study participation, limits compliance with study procedures or substantially increases the risk of incurring adverse events, including:; Bleeding diathesis or active hemorrhage,; Active infection,; Child-Pugh class B or C cirrhosis,; Known pulmonary disease with significant impact in lung function; Oncologic emergencies or complications (e.g., malignant hypercalcemia, superior vena cava syndrome, carcinoid syndrome that is unstable and with available alternative therapies),; Psychiatric or abuse condition; Infectious colitis Grade >=2 not resolved to Grade 1 within 72 hours within the past 3 months.
Unknown, judged by first model only
No facts provided regarding uncontrolled concomitant illnesses or specific contraindications.
I20 Have LVEF <50% by either echocardiography or multi-gated acquisition (scanning) within 28 days before randomization/enrollment.
Unknown, judged by first model only
No LVEF data provided in facts.
I21 Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.
Unknown, judged by first model only
No facts provided regarding pleural, ascites, or pericardial effusions.
I22 Have a history of (non-infectious) interstitial lung disease (ILD) /pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. Asymptomatic interstitial changes caused by previous radiation therapy, chemotherapy, or other factors such as smoking are acceptable.
Unknown, judged by first model only
No facts provided regarding history of ILD or pneumonitis.
I23 Are a participant of child-bearing potential who are pregnant or breastfeeding or are planning pregnancy within 225 days (~7.5 months) after receiving last dose of BNT326 and within 6 months after last dose of pumitamig, whichever is longer.
At screening, judged by code
Confirmed at screening (consent, pregnancy or protocol).
I24 Are potentially fertile males, who are planning to father children during the study or within 135 days (~4.5 months) after the last dose of BNT326 and within 6 months after last dose of pumitamig, whichever is longer.
Unknown, judged by first model only
No facts provided regarding fertility plans or contraception status.
I25 Are subject to exclusion periods from another investigational study.
Unknown, judged by first model only
No facts provided regarding participation in other investigational studies.
I26 Specific to pumitamig: Participants with significant risks of hemorrhage or evidence of major coagulation disorders as specified in the protocol.
Unknown, judged by first model only
No facts provided regarding hemorrhage risk or coagulation disorders.
I27 Specific to pumitamig: Have a history of intolerance to treatment with an anti-vascular endothelial growth factor, anti-PD-1/PDL-1, or similar substance, including, but not limited to, bevacizumab, ramucirumab, atezolizumab, pembrolizumab, nivolumab, or other related therapies.
Unknown, judged by first model only
No facts provided regarding intolerance to anti-VEGF or anti-PD-1/PD-L1 agents.
I28 Cohort 1E: Have histological diagnosis of fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC. NOTE: Other protocol defined Inclusion/Exclusion criteria apply.
Models disagree, judged by models disagree, using F2
Writer said not met, checker said unknown. Patient has NSCLC, not HCC or cholangiocarcinoma.
Not eligible Study of Izalontamab Brengitecan (BMS-986507) Versus Platinum-Pemetrexed for EGFR-mutated Non-small Cell Lung Cancer After Failure of EGFR TKI Therapy (IZABRIGHT-Lung01) I2 Not metI3 Not metE2 Models disagreeE4 At screeningAGE-MIN MetI1 MetI4 MetE1 Does not applyE3 Does not apply Phase 2, Phase 3, Bristol-Myers Squibb. Nearest site: Baden, Switzerland, 21 km away. 1 question to clarify.
Ask before referring
- E2 Leptomeningeal metastases or spinal cord compression.Writer said does not apply, checker said unknown. No brain metastases on baseline MRI implies no leptomeningeal disease.
What rules the patient out
- I2 Documented evidence of EGFR mutation (exon 19 deletion, L858R mutation).Patient has EGFR exon 20 insertion, not exon 19 del or L858R.
- I3 Progressive disease on a 3rd-generation (such as osimertinib, furmonertinib, lazertinib,...) EGFR-TKI-based mono- or combination therapy regimen as the most recent line of therapy in an adjuvant, locally advanced, or metastatic treatment setting.No prior systemic treatment, so no progression on 3rd-gen EGFR-TKI.
Every criterion, as written in the registry
AGE-MIN Age at least 18 years
Met, judged by code, using F1
I1 Non-squamous NSCLC, not amenable to treatment in curative intent.
Met, judged by both models, using F2
Stage IV non-squamous NSCLC is not amenable to curative intent.
I2 Documented evidence of EGFR mutation (exon 19 deletion, L858R mutation).
Not met, judged by both models, using F3
Patient has EGFR exon 20 insertion, not exon 19 del or L858R.
I3 Progressive disease on a 3rd-generation (such as osimertinib, furmonertinib, lazertinib,...) EGFR-TKI-based mono- or combination therapy regimen as the most recent line of therapy in an adjuvant, locally advanced, or metastatic treatment setting.
Not met, judged by both models, using F4
No prior systemic treatment, so no progression on 3rd-gen EGFR-TKI.
I4 Eligible to receive a platinum-based doublet chemotherapy regimen (either cisplatin or carboplatin in combination with pemetrexed).
Met, judged by both models, using F8
Adequate organ function and bone marrow reserve for chemotherapy.
E1 Inadequate organ function and/or bone marrow reserve.
Does not apply, judged by both models, using F8
Lab values show adequate organ function and bone marrow reserve.
E2 Leptomeningeal metastases or spinal cord compression.
Models disagree, judged by models disagree, using F5
Writer said does not apply, checker said unknown. No brain metastases on baseline MRI implies no leptomeningeal disease.
E3 Poorly controlled systemic medical conditions.
Does not apply, judged by both models, using F11
Diabetes is controlled, so not poorly controlled.
E4 Other protocol-defined inclusion/exclusion criteria apply.
At screening, judged by code
Confirmed at screening (consent, pregnancy or protocol).
Not eligible A Study of Clinical Outcomes in Participants With EGFR Mutated Advanced Non-Small Cell Lung Cancer (NSCLC) in a Real-World Setting I1 Not metE3 Models disagreeE4 Models disagreeI3 UnknownI4 UnknownI2 At screeningAGE-MIN MetE1 Does not applyE2 Does not apply Phase not given, Janssen Research & Development, LLC. Nearest site: Konstanz, Germany, 57 km away. 4 questions to clarify.
Ask before referring
- I3 Participant is being planned to be initiated with an amivantamab-containing regimen for the first time within 4 weeks following the visit for start of data collectionNo facts confirm the specific timing of regimen initiation relative to enrollment.
- I4 Decision to administer an amivantamab-containing regimen has been made prior to participant's enrollment in the study and is separate from the physician's decision to include the participant in the current studyNo facts confirm the decision was made prior to enrollment.
- E3 Participants who are not receiving amivantamab but are being treated with a biosimilar or a non-original biologic agentWriter said does not apply, checker said unknown. No prior systemic treatment implies no current biosimilar or non-original biologic use.
- E4 Participants with conditions listed in the contraindications of the SmPC for amivantamab or other agents essential for the applicable amivantamab-containing treatment regimen (lazertinib/ platinum/ pemetrexed)Writer said does not apply, checker said unknown. Labs normal, no ILD or active infection, no known contraindications.
What rules the patient out
- I1 Participant has a confirmed diagnosis of common epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) (EGFR exon 19 deletions or exon 21 L858R substitution) and is eligible for an amivantamab-containing regimen per the judgment of the treating physician and in alignment with the approved amivantamab indications and recommended prophylactic and reactive medication as described in the local specific summary of product characteristics (SmPC) for amivantamabPatient has EGFR exon 20 insertion, not exon 19 del or L858R.
Every criterion, as written in the registry
AGE-MIN Age at least 18 years
Met, judged by code, using F1
I1 Participant has a confirmed diagnosis of common epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) (EGFR exon 19 deletions or exon 21 L858R substitution) and is eligible for an amivantamab-containing regimen per the judgment of the treating physician and in alignment with the approved amivantamab indications and recommended prophylactic and reactive medication as described in the local specific summary of product characteristics (SmPC) for amivantamab
Not met, judged by both models, using F3
Patient has EGFR exon 20 insertion, not exon 19 del or L858R.
I2 Participants or their legally acceptable representative, where applicable, must sign a participation agreement/Informed consent form (ICF) allowing source data verification in accordance with local requirements
At screening, judged by code
Confirmed at screening (consent, pregnancy or protocol).
I3 Participant is being planned to be initiated with an amivantamab-containing regimen for the first time within 4 weeks following the visit for start of data collection
Unknown, judged by first model only
No facts confirm the specific timing of regimen initiation relative to enrollment.
I4 Decision to administer an amivantamab-containing regimen has been made prior to participant's enrollment in the study and is separate from the physician's decision to include the participant in the current study
Unknown, judged by first model only
No facts confirm the decision was made prior to enrollment.
E1 At the time of the initiation of the amivantamab-containing regimen, the participant is receiving an active systemic anticancer treatment for advanced NSCLC that is not included in the locally approved combination regimen with amivantamab (regardless of whether it is part of an interventional study). One cycle of platinum-based chemotherapy (for example, carboplatin-pemetrexed) is permitted prior to the first dose of amivantamab in a 1L while awaiting biopsy results
Does not apply, judged by both models, using F4
No prior systemic treatment means no active non-approved regimen is being received.
E2 Participant has received prior treatment with amivantamab in a clinical trial or for compassionate use
Does not apply, judged by both models, using F4
No prior systemic treatment implies no prior amivantamab exposure.
E3 Participants who are not receiving amivantamab but are being treated with a biosimilar or a non-original biologic agent
Models disagree, judged by models disagree, using F4
Writer said does not apply, checker said unknown. No prior systemic treatment implies no current biosimilar or non-original biologic use.
E4 Participants with conditions listed in the contraindications of the SmPC for amivantamab or other agents essential for the applicable amivantamab-containing treatment regimen (lazertinib/ platinum/ pemetrexed)
Models disagree, judged by models disagree, using F8 F9 F10
Writer said does not apply, checker said unknown. Labs normal, no ILD or active infection, no known contraindications.
Not eligible A Study to Learn More About How Well Sevabertinib Works and How Safe it is Compared With Standard Treatment, in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2) E2 Applies, excludesI3 Models disagreeI5 UnknownE1 UnknownE3 UnknownE4 UnknownE5 UnknownE6 UnknownAGE-MIN MetI1 MetI2 MetI4 Met Phase 3, Bayer. Nearest site: Fribourg, Switzerland, 123 km away. 7 questions to clarify.
Ask before referring
- I3 Documented activating HER2 mutation in the tyrosine kinase domain (TKD) assessed by tissue molecular test in a CLIA-certified (US sites) or an equally accredited (outside of the US) local laboratory. However, participants may be included at the discretion of the investigator if the laboratory performing the assay is not CLIA or similar certified but the laboratory is locally accredited.Writer said not met, checker said unknown. Patient has EGFR mutation, not the required HER2 TKD mutation.
- I5 Eligible to receive treatment with the selected platinum-based doublet-chemotherapy (i.e. cisplatin/pemetrexed or carboplatin/pemetrexed) and pembrolizumab in accordance with the SmPC/Product Information.Facts do not specify contraindications to platinum/pemetrexed/pembrolizumab per SmPC.
- E1 Known history of prior malignancy except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for five years since initiation of that therapy. Exception: the following cancer types are acceptable within five years if curatively treated or under surveillance:; a. in situ cancers of cervix, breast, or skin,; b. superficial bladder cancer (Ta, Tis and T1),; c. limited-stage prostate cancer,; d. basal or squamous cancers of the skin.Answer cited no patient fact.
- E3 Inability to discontinue treatment with chronic systemic corticosteroids. Participants who require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study. Replacement therapy (e.g., physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is acceptable, provided that the dose is stable for >4 weeks prior to planned start of study intervention.Answer cited no patient fact.
- E4 Pre-existing peripheral neuropathy that is Grade >=2 by CTCAE (v5.0).Answer cited no patient fact.
- E5 History of severe hypersensitivity reaction to treatment with a monoclonal antibody.Answer cited no patient fact.
- E6 Prior radiotherapy outside of the brain within 21 days before of planned start of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.Answer cited no patient fact.
What rules the patient out
- E2 Tumors with targetable alterations with approved available therapy, with the exception of HER2 mutation in the TKD.EGFR mutation is a targetable alteration with approved therapy, excluding the patient.
Every criterion, as written in the registry
AGE-MIN Age at least 18 years
Met, judged by code, using F1
I1 Participant must be >=18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signing the informed consent.
Met, judged by both models, using F1
Patient is 54 years old, which is greater than 18.
I2 Documented histologically or cytologically confirmed locally advanced non-squamous NSCLC, not suitable for definitive therapy or metastatic non-squamous NSCLC at screening (small cell or mixed histologies are excluded) (Stage III-IV NSCLC).
Met, judged by both models, using F2
Stage IV non-squamous NSCLC (adenocarcinoma) is documented.
I3 Documented activating HER2 mutation in the tyrosine kinase domain (TKD) assessed by tissue molecular test in a CLIA-certified (US sites) or an equally accredited (outside of the US) local laboratory. However, participants may be included at the discretion of the investigator if the laboratory performing the assay is not CLIA or similar certified but the laboratory is locally accredited.
Models disagree, judged by models disagree, using F3
Writer said not met, checker said unknown. Patient has EGFR mutation, not the required HER2 TKD mutation.
I4 No prior systemic therapy for locally advanced or metastatic disease. No prior treatment with a HER2 ex20ins-targeted therapy (e.g. poziotinib, trastuzumab deruxtecan). Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the start of screening.
Met, judged by both models, using F4
No prior systemic therapy for advanced disease is reported.
I5 Eligible to receive treatment with the selected platinum-based doublet-chemotherapy (i.e. cisplatin/pemetrexed or carboplatin/pemetrexed) and pembrolizumab in accordance with the SmPC/Product Information.
Unknown, judged by first model only
Facts do not specify contraindications to platinum/pemetrexed/pembrolizumab per SmPC.
E1 Known history of prior malignancy except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for five years since initiation of that therapy. Exception: the following cancer types are acceptable within five years if curatively treated or under surveillance:; a. in situ cancers of cervix, breast, or skin,; b. superficial bladder cancer (Ta, Tis and T1),; c. limited-stage prostate cancer,; d. basal or squamous cancers of the skin.
Unknown, judged by first model only
Answer cited no patient fact.
E2 Tumors with targetable alterations with approved available therapy, with the exception of HER2 mutation in the TKD.
Applies, excludes, judged by both models, using F3
EGFR mutation is a targetable alteration with approved therapy, excluding the patient.
E3 Inability to discontinue treatment with chronic systemic corticosteroids. Participants who require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study. Replacement therapy (e.g., physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is acceptable, provided that the dose is stable for >4 weeks prior to planned start of study intervention.
Unknown, judged by first model only
Answer cited no patient fact.
E4 Pre-existing peripheral neuropathy that is Grade >=2 by CTCAE (v5.0).
Unknown, judged by first model only
Answer cited no patient fact.
E5 History of severe hypersensitivity reaction to treatment with a monoclonal antibody.
Unknown, judged by first model only
Answer cited no patient fact.
E6 Prior radiotherapy outside of the brain within 21 days before of planned start of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.
Unknown, judged by first model only
Answer cited no patient fact.
Not eligible A Study to Assess Zipalertinib Versus Placebo in Participants With Early Stage NSCLC With Uncommon EGFR Mutations, Following Complete Tumor Resection I4 Not metI5 Not metI7 Not metI2 Models disagreeI8 Models disagreeE3 Models disagreeE1 UnknownE5 UnknownE6 UnknownE8 UnknownE9 UnknownAGE-MIN MetI1 MetI3 MetI6 MetE2 Does not applyE4 Does not applyE7 Does not apply Phase 3, Taiho Oncology, Inc.. Nearest site: Mulhouse, France, 100 km away. 8 questions to clarify.
Ask before referring
- I2 Documented EGFRmt status as determined by local testing performed at a clinical laboratory improvement amendment (CLIA) certified (United States [US]) or accredited (outside of the US) local laboratory, defined as either one of the following EGFRmt:; exon20 insertion mutations (ex20ins) or; other uncommon, non-ex20ins EGFRmt (eg, G719X, L861Q, or S768I) exons 18-21 of the EGFR tyrosine kinase domainWriter said met, checker said unknown. EGFR exon 20 insertion mutation detected via next-generation sequencing.
- I8 Archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers.Writer said met, checker said unknown. Tissue NGS was performed, indicating sufficient archival tumor tissue was available.
- E1 Is currently receiving an investigational drug in a clinical trial or participating in any other type of medical research.Answer cited no patient fact.
- E3 Has received only wedge resections (complete anatomic segmentectomy is acceptable).Writer said does not apply, checker said unknown. Patient has stage IV disease, so no resection (wedge or otherwise) was performed.
- E5 Unable to swallow tablets or has any disease or condition that may significantly affect gastrointestinal (GI) absorption of zipalertinib (such as inflammatory bowel disease, malabsorption syndrome, or prior significant bowel resection).Answer cited no patient fact.
- E6 Has a history of any other cancer except for any of the following:; Non-melanoma skin cancer treated with curative intent; Carcinoma in situ treated with curative intent; Other curatively treated cancer, with no evidence of disease for >3 years following the end of treatment and, in the opinion of the treating physician, has no substantial risk of recurrence.; Concurrent malignancy of which natural history does not have the potential to interfere with the safety or efficacy assessment (eg, Gleason 6 prostate cancer)Answer cited no patient fact.
- E8 Active bleeding disorders.Answer cited no patient fact.
- E9 Known hypersensitivity to the ingredients in zipalertinib/placebo or any drugs similar in structure or class.Answer cited no patient fact.
What rules the patient out
- I4 Complete surgical resection of the primary NSCLC is mandatory with negative surgical margins and systematic lymph node sampling or dissection.Patient has stage IV disease, implying no complete surgical resection of primary tumor.
- I5 Complete recovery from surgery, including post-operative wound healing, and prior adjuvant chemotherapy (if applicable) at the time of randomization. Randomization timing is defined as follows:; For participants without prior adjuvant chemotherapy: 4 weeks and 12 weeks following surgery.; For participants with prior adjuvant chemotherapy: 4 weeks and 8 weeks after the last dose of adjuvant chemotherapy.Patient has stage IV disease, so complete surgical resection and recovery did not occur.
- I7 Pathologic (post-operative) Stage IB, IIA, IIB, or IIIA according to the AJCC 9th tumor nodes metastasis (TNM) staging system for lung cancer. In addition, participants with stage IIIB are eligible when regional lymph node involvement is N2.Patient is stage IV, which is outside the eligible stages IB-IIIa/N2 IIIB.
Every criterion, as written in the registry
AGE-MIN Age at least 18 years
Met, judged by code, using F1
I1 Histologically confirmed diagnosis of primary NSCLC on predominantly non-squamous histology.
Met, judged by both models, using F2
Patient has histologically confirmed non-small cell lung cancer, adenocarcinoma (non-squamous).
I2 Documented EGFRmt status as determined by local testing performed at a clinical laboratory improvement amendment (CLIA) certified (United States [US]) or accredited (outside of the US) local laboratory, defined as either one of the following EGFRmt:; exon20 insertion mutations (ex20ins) or; other uncommon, non-ex20ins EGFRmt (eg, G719X, L861Q, or S768I) exons 18-21 of the EGFR tyrosine kinase domain
Models disagree, judged by models disagree, using F3
Writer said met, checker said unknown. EGFR exon 20 insertion mutation detected via next-generation sequencing.
I3 Baseline imaging assessment of the brain (MRI [preferred modality] or CT scan) performed within 8 weeks prior to randomization must show no evidence of brain metastasis
Met, judged by both models, using F5
Baseline MRI shows no evidence of brain metastasis.
I4 Complete surgical resection of the primary NSCLC is mandatory with negative surgical margins and systematic lymph node sampling or dissection.
Not met, judged by both models, using F2
Patient has stage IV disease, implying no complete surgical resection of primary tumor.
I5 Complete recovery from surgery, including post-operative wound healing, and prior adjuvant chemotherapy (if applicable) at the time of randomization. Randomization timing is defined as follows:; For participants without prior adjuvant chemotherapy: 4 weeks and 12 weeks following surgery.; For participants with prior adjuvant chemotherapy: 4 weeks and 8 weeks after the last dose of adjuvant chemotherapy.
Not met, judged by both models, using F2
Patient has stage IV disease, so complete surgical resection and recovery did not occur.
I6 Eastern cooperative oncology group performance status (ECOG PS) of 0 or 1.
Met, judged by both models, using F6
ECOG performance status is 0, which is within the required range.
I7 Pathologic (post-operative) Stage IB, IIA, IIB, or IIIA according to the AJCC 9th tumor nodes metastasis (TNM) staging system for lung cancer. In addition, participants with stage IIIB are eligible when regional lymph node involvement is N2.
Not met, judged by both models, using F2
Patient is stage IV, which is outside the eligible stages IB-IIIa/N2 IIIB.
I8 Archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers.
Models disagree, judged by models disagree, using F3
Writer said met, checker said unknown. Tissue NGS was performed, indicating sufficient archival tumor tissue was available.
E1 Is currently receiving an investigational drug in a clinical trial or participating in any other type of medical research.
Unknown, judged by first model only
Answer cited no patient fact.
E2 Treatment with any of the following within the time frame specified:; Zipalertinib (TAS6417/CLN-081) or any other EGFR inhibitor at any time.; Pre-operative or post-operative or planned radiation therapy for the current lung cancer.; Any prior systemic anticancer therapy for NSCLC, including preoperative (neoadjuvant) chemotherapy, immunotherapy, or investigational therapy. (Exception: Participants who have received postoperative adjuvant platinum-based chemotherapy up to 4 cycles are permitted); Major surgery (including primary tumor surgery, excluding placement of vascular access) within 4 weeks prior to the first dose of study treatment.; Treatment with an investigational drug within five half-lives of the compound or any of its related material, if known.
Does not apply, judged by both models, using F4
No prior systemic treatment, radiation, or major surgery mentioned in facts.
E3 Has received only wedge resections (complete anatomic segmentectomy is acceptable).
Models disagree, judged by models disagree, using F2
Writer said does not apply, checker said unknown. Patient has stage IV disease, so no resection (wedge or otherwise) was performed.
E4 Past medical history of interstitial lung disease (ILD)/pneumonitis, drug-induced ILD/pneumonitis or any evidence of clinically active ILD/pneumonitis.
Does not apply, judged by both models, using F9
No history of interstitial lung disease or pneumonitis.
E5 Unable to swallow tablets or has any disease or condition that may significantly affect gastrointestinal (GI) absorption of zipalertinib (such as inflammatory bowel disease, malabsorption syndrome, or prior significant bowel resection).
Unknown, judged by first model only
Answer cited no patient fact.
E6 Has a history of any other cancer except for any of the following:; Non-melanoma skin cancer treated with curative intent; Carcinoma in situ treated with curative intent; Other curatively treated cancer, with no evidence of disease for >3 years following the end of treatment and, in the opinion of the treating physician, has no substantial risk of recurrence.; Concurrent malignancy of which natural history does not have the potential to interfere with the safety or efficacy assessment (eg, Gleason 6 prostate cancer)
Unknown, judged by first model only
Answer cited no patient fact.
E7 Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) that is unstable or not controlled with treatment.
Does not apply, judged by both models, using F10
HIV, hepatitis B, and C are negative.
E8 Active bleeding disorders.
Unknown, judged by first model only
Answer cited no patient fact.
E9 Known hypersensitivity to the ingredients in zipalertinib/placebo or any drugs similar in structure or class.
Unknown, judged by first model only
Answer cited no patient fact.
Not eligible A Prospective Cohort Study to Evaluate Molecular pRognostic Factors and Resistance Mechanisms to Osimertinib in Adjuvant Treatment of Completely Resected pIB-IIIA Non-small Cell Lung Carcinoma With Common EGFR Mutations (L858R and Del19) I4 Not metI5 Not metI3 Models disagreeI7 Models disagreeE1 Models disagreeE3 Models disagreeI6 UnknownI8 UnknownI9 UnknownI10 UnknownI11 UnknownI12 UnknownI1 At screeningE4 At screeningAGE-MIN MetI2 MetE2 Does not applyE5 Does not apply n/a, Intergroupe Francophone de Cancerologie Thoracique. Nearest site: Colmar, France, 118 km away. 10 questions to clarify.
Ask before referring
- I3 Pre-surgical disease evaluation including brain MRI/CT-scan and total body PET-FDG CT-scan prior to surgery.Writer said not met, checker said unknown. Patient has stage IV disease, not pre-surgical stage I-III, so pre-surgical evaluation is not applicable.
- I6 Archival tumour tissue FFPE blocks from surgery available for centrally molecular analyses.No information provided about availability of archival FFPE tissue blocks.
- I7 Patient eligible to receive osimertinib adjuvant therapy in a 3-year intent to treat decision; patients could receive if necessary adjuvant chemotherapy before starting osimertinib treatment.Writer said not met, checker said unknown. Patient has stage IV disease, not eligible for adjuvant therapy which is for resected disease.
- I8 Patient who is capable, according to the investigator, of complying with the study's requirements and restrictions.Investigator assessment of compliance capability is not provided in facts.
- I9 Patient followed in the institution on a regular basis (every 3 to 6 months) according to standard recommendations.No information provided about the patient's follow-up schedule or institution.
- I10 Estimated life expectancy > 3 years.Estimated life expectancy is not explicitly stated in the facts.
- I11 Woman patients who are of childbearing potential are eligible:; They must have a negative pregnancy test before the first dose of osimertinib.; They must agree to use effective methods of contraception throughout the course of treatment and should be maintained for 2 months after the end of treatment.Invalid answer 'does_not_apply'.
- I12 Male subjects who are sexually active with a woman of childbearing potential are eligible if an efficacious contraception method should be used during the treatment and during the 4 months following the last dose.No information provided about sexual activity or contraception status.
- E1 History of cancer, except for the following situations: Patients with history of cancer for more than 3 years are eligible if they have been treated and considered cured. Patients with history of in situ carcinoma of the cervix or non-melanoma skin carcinoma are eligible.Writer said does not apply, checker said unknown. No history of prior cancer mentioned; current diagnosis is the primary cancer.
- E3 Incompletely resected NSCLC (R1 or R2).Writer said does not apply, checker said unknown. Patient has stage IV disease and no resection mentioned, so incomplete resection is not applicable.
What rules the patient out
- I4 Histologically complete anatomical resection (R0) of stage pIB-IIIA (pTNM 8th edition) NSCLC.Patient has stage IV disease, not stage pIB-IIIA, and no resection mentioned.
- I5 Presence of a common EGFR mutation (Del19 or L858R).Patient has EGFR exon 20 insertion, not Del19 or L858R.
Every criterion, as written in the registry
AGE-MIN Age at least 18 years
Met, judged by code, using F1
I1 Signed Informed consent.
At screening, judged by code
Confirmed at screening (consent, pregnancy or protocol).
I2 Age >= 18 years.
Met, judged by both models, using F1
Patient is 54 years old, which is greater than or equal to 18.
I3 Pre-surgical disease evaluation including brain MRI/CT-scan and total body PET-FDG CT-scan prior to surgery.
Models disagree, judged by models disagree, using F2
Writer said not met, checker said unknown. Patient has stage IV disease, not pre-surgical stage I-III, so pre-surgical evaluation is not applicable.
I4 Histologically complete anatomical resection (R0) of stage pIB-IIIA (pTNM 8th edition) NSCLC.
Not met, judged by both models, using F2
Patient has stage IV disease, not stage pIB-IIIA, and no resection mentioned.
I5 Presence of a common EGFR mutation (Del19 or L858R).
Not met, judged by both models, using F3
Patient has EGFR exon 20 insertion, not Del19 or L858R.
I6 Archival tumour tissue FFPE blocks from surgery available for centrally molecular analyses.
Unknown, judged by first model only
No information provided about availability of archival FFPE tissue blocks.
I7 Patient eligible to receive osimertinib adjuvant therapy in a 3-year intent to treat decision; patients could receive if necessary adjuvant chemotherapy before starting osimertinib treatment.
Models disagree, judged by models disagree, using F2
Writer said not met, checker said unknown. Patient has stage IV disease, not eligible for adjuvant therapy which is for resected disease.
I8 Patient who is capable, according to the investigator, of complying with the study's requirements and restrictions.
Unknown, judged by first model only
Investigator assessment of compliance capability is not provided in facts.
I9 Patient followed in the institution on a regular basis (every 3 to 6 months) according to standard recommendations.
Unknown, judged by first model only
No information provided about the patient's follow-up schedule or institution.
I10 Estimated life expectancy > 3 years.
Unknown, judged by first model only
Estimated life expectancy is not explicitly stated in the facts.
I11 Woman patients who are of childbearing potential are eligible:; They must have a negative pregnancy test before the first dose of osimertinib.; They must agree to use effective methods of contraception throughout the course of treatment and should be maintained for 2 months after the end of treatment.
Unknown, judged by first model only
Invalid answer 'does_not_apply'.
I12 Male subjects who are sexually active with a woman of childbearing potential are eligible if an efficacious contraception method should be used during the treatment and during the 4 months following the last dose.
Unknown, judged by first model only
No information provided about sexual activity or contraception status.
E1 History of cancer, except for the following situations: Patients with history of cancer for more than 3 years are eligible if they have been treated and considered cured. Patients with history of in situ carcinoma of the cervix or non-melanoma skin carcinoma are eligible.
Models disagree, judged by models disagree, using F2
Writer said does not apply, checker said unknown. No history of prior cancer mentioned; current diagnosis is the primary cancer.
E2 Neoadjuvant anti-cancer treatment (osimertinib and/or chemotherapy or other anti-cancer treatment).
Does not apply, judged by both models, using F4
No prior systemic treatment for advanced disease, implying no neoadjuvant therapy.
E3 Incompletely resected NSCLC (R1 or R2).
Models disagree, judged by models disagree, using F2
Writer said does not apply, checker said unknown. Patient has stage IV disease and no resection mentioned, so incomplete resection is not applicable.
E4 Any medical condition that would, according to the investigator's judgment, prevent the patient's participation in the clinical study.
At screening, judged by code
Confirmed at screening (consent, pregnancy or protocol).
E5 Active infection (e.g. patients receiving treatment for infection) including hepatitis C virus (HCV) and human immunodeficiency virus (HIV), or active uncontrolled hepatitis B infection except for the situations described in APPENDIX I. Screening for chronic conditions is not required.
Does not apply, judged by both models, using F10
No active infection and negative HIV/Hepatitis B/C status.
Not eligible A Study to Assess Disease Activity and Adverse Events of Intravenous (IV) Telisotuzumab Vedotin Compared to IV Docetaxel in Adult Participants With Previously Treated Non-Squamous Non-Small Cell Lung Cancer (NSCLC) I5 Not metI10 Not metE4 Applies, excludesE2 Models disagreeE5 Models disagreeE6 Models disagreeI1 UnknownI2 UnknownI3 UnknownI6 UnknownI11 UnknownI12 UnknownE7 UnknownE10 UnknownE11 UnknownAGE-MIN MetI4 MetI7 MetI8 MetI9 MetE1 Does not applyE3 Does not applyE8 Does not applyE9 Does not apply Phase 3, AbbVie. Nearest site: Feldkirch, Austria, 81 km away. 12 questions to clarify.
Ask before referring
- I1 Projected life expectancy of at least 12 weeks.Life expectancy is a clinical projection not explicitly stated in the provided facts.
- I2 Participants must have c-Met overexpressing non-small cell lung cancer (NSCLC) as assessed by an AbbVie designated immunohistochemistry (IHC) laboratory using the VENTANA MET (SP44) RxDx assay.No data provided regarding c-Met overexpression status via the specified IHC assay.
- I3 Archival or fresh tumor material must be submitted for assessment of c-Met protein expression levels during the Pre-Screening period. Tumor material from the primary tumor site and/or metastatic sites are allowed.; If a participant was prescreened for Study M14-239 but did not enroll, tumor material previously submitted for Study M14-239 may be used for Study M18-868 Pre-Screening upon confirmation from AbbVie that sufficient evaluable tumor material is available (Except China).Facts do not confirm if tumor material was submitted for c-Met assessment.
- I6 Actionable alterations in genes other than EGFR are eligible.No information provided about actionable alterations in genes other than EGFR.
- I11 Must be considered appropriate for docetaxel therapy based on the assessment of the treating physician.Physician assessment regarding suitability for docetaxel is not provided in the facts.
- I12 Participants with metastases to the central nervous system (CNS) are eligible only after adequate treatment (such as surgery, radiotherapy, or drug therapy) is provided and:; They are asymptomatic and off or on a stable or reducing dose of systemic steroids (on no more than 10 mg per day [QD] prednisone or equivalent) and/or anticonvulsants for at least 2 weeks prior to randomization.Invalid answer 'does_not_apply'.
- E2 Evidence of leptomeningeal disease.Writer said does not apply, checker said unknown. No evidence of leptomeningeal disease is reported in the facts.
- E5 Participants who have received prior c-Met-targeted antibodies, prior telisotuzumab vedotin, or prior antibody-drug conjugates either targeting c-Met or consisting of monomethylauristatin E..Writer said does not apply, checker said unknown. No prior systemic treatment means no prior c-Met targeted antibodies or ADCs.
- E6 Participants who have received prior docetaxel therapy.Writer said does not apply, checker said unknown. No prior systemic treatment means no prior docetaxel therapy.
- E7 A history of other malignancies except:; Malignancy treated with curative intent and with no known active disease present for >=2 years before the first dose of study drug and felt to be at low risk for recurrence by investigator. Additionally, participants must not be receiving any ongoing anti-cancer therapy, including maintenance therapy, prior to randomization..; Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.; Adequately treated carcinoma in situ without current evidence of disease.Answer cited no patient fact.
- E10 Major surgery within 21 days prior to randomization.Answer cited no patient fact.
- E11 Clinically significant condition(s) as listed in the protocol.Specific protocol-defined clinically significant conditions are not detailed in the facts.
What rules the patient out
- I5 A known epidermal growth factor receptor (EGFR) activating mutation status. -- Participants with EGFR activating mutations are not eligiblePatient has an EGFR mutation, and participants with EGFR activating mutations are not eligible.
- I10 Have progressed on at least 1 line of prior therapy for locally advanced/metastatic NSCLC; Participants WITHOUT an actionable gene alteration: must have progressed on (or be considered ineligible for) platinum-based chemotherapy and immune checkpoint inhibitor (as monotherapy or in combination with chemotherapy).; Participants WITH an actionable gene alteration for which immune checkpoint inhibitor therapy is not standard of care (e.g., anaplastic lymphoma kinase [ALK] translocation): must have progressed on (or be considered ineligible for) anti-cancer therapy targeting driver gene alterations and platinum-based chemotherapy.; Participants with gene alterations for which immune checkpoint inhibitor is standard of care must have also progressed on (or be considered ineligible for) immune checkpoint inhibitor (as monotherapy or in combination with chemotherapy).Patient has not progressed on at least 1 line of prior therapy as they are treatment-naive.
- E4 Epidermal growth factor receptor (EGFR) activating mutations.Patient has an EGFR exon 20 insertion mutation, which is an EGFR activating mutation.
Every criterion, as written in the registry
AGE-MIN Age at least 18 years
Met, judged by code, using F1
I1 Projected life expectancy of at least 12 weeks.
Unknown, judged by first model only
Life expectancy is a clinical projection not explicitly stated in the provided facts.
I2 Participants must have c-Met overexpressing non-small cell lung cancer (NSCLC) as assessed by an AbbVie designated immunohistochemistry (IHC) laboratory using the VENTANA MET (SP44) RxDx assay.
Unknown, judged by first model only
No data provided regarding c-Met overexpression status via the specified IHC assay.
I3 Archival or fresh tumor material must be submitted for assessment of c-Met protein expression levels during the Pre-Screening period. Tumor material from the primary tumor site and/or metastatic sites are allowed.; If a participant was prescreened for Study M14-239 but did not enroll, tumor material previously submitted for Study M14-239 may be used for Study M18-868 Pre-Screening upon confirmation from AbbVie that sufficient evaluable tumor material is available (Except China).
Unknown, judged by first model only
Facts do not confirm if tumor material was submitted for c-Met assessment.
I4 A histologically or cytologically documented non-squamous cell NSCLC that is locally advanced or metastatic.
Met, judged by both models, using F2
Patient has documented non-squamous NSCLC (adenocarcinoma) that is stage IV (metastatic).
I5 A known epidermal growth factor receptor (EGFR) activating mutation status. -- Participants with EGFR activating mutations are not eligible
Not met, judged by both models, using F3
Patient has an EGFR mutation, and participants with EGFR activating mutations are not eligible.
I6 Actionable alterations in genes other than EGFR are eligible.
Unknown, judged by first model only
No information provided about actionable alterations in genes other than EGFR.
I7 Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Met, judged by both models, using F7
Patient has measurable disease defined by RECIST 1.1 criteria.
I8 An Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
Met, judged by both models, using F6
ECOG performance status is 0, which falls within the required 0-1 range.
I9 Have received no more than 1 line of prior systemic cytotoxic chemotherapy in the locally advanced or metastatic setting.
Met, judged by both models, using F4
Patient has received no prior systemic treatment, which is no more than 1 line.
I10 Have progressed on at least 1 line of prior therapy for locally advanced/metastatic NSCLC; Participants WITHOUT an actionable gene alteration: must have progressed on (or be considered ineligible for) platinum-based chemotherapy and immune checkpoint inhibitor (as monotherapy or in combination with chemotherapy).; Participants WITH an actionable gene alteration for which immune checkpoint inhibitor therapy is not standard of care (e.g., anaplastic lymphoma kinase [ALK] translocation): must have progressed on (or be considered ineligible for) anti-cancer therapy targeting driver gene alterations and platinum-based chemotherapy.; Participants with gene alterations for which immune checkpoint inhibitor is standard of care must have also progressed on (or be considered ineligible for) immune checkpoint inhibitor (as monotherapy or in combination with chemotherapy).
Not met, judged by both models, using F4
Patient has not progressed on at least 1 line of prior therapy as they are treatment-naive.
I11 Must be considered appropriate for docetaxel therapy based on the assessment of the treating physician.
Unknown, judged by first model only
Physician assessment regarding suitability for docetaxel is not provided in the facts.
I12 Participants with metastases to the central nervous system (CNS) are eligible only after adequate treatment (such as surgery, radiotherapy, or drug therapy) is provided and:; They are asymptomatic and off or on a stable or reducing dose of systemic steroids (on no more than 10 mg per day [QD] prednisone or equivalent) and/or anticonvulsants for at least 2 weeks prior to randomization.
Unknown, judged by first model only
Invalid answer 'does_not_apply'.
E1 Evidence of new, untreated CNS metastases or progressing CNS metastases after treatment.
Does not apply, judged by both models, using F5
No evidence of new or untreated CNS metastases; baseline MRI is negative.
E2 Evidence of leptomeningeal disease.
Models disagree, judged by models disagree, using F5
Writer said does not apply, checker said unknown. No evidence of leptomeningeal disease is reported in the facts.
E3 Participants with adenosquamous or neuroendocrine histology, nor sarcomatoid features.
Does not apply, judged by both models, using F2
Histology is adenocarcinoma, not adenosquamous, neuroendocrine, or sarcomatoid.
E4 Epidermal growth factor receptor (EGFR) activating mutations.
Applies, excludes, judged by both models, using F3
Patient has an EGFR exon 20 insertion mutation, which is an EGFR activating mutation.
E5 Participants who have received prior c-Met-targeted antibodies, prior telisotuzumab vedotin, or prior antibody-drug conjugates either targeting c-Met or consisting of monomethylauristatin E..
Models disagree, judged by models disagree, using F4
Writer said does not apply, checker said unknown. No prior systemic treatment means no prior c-Met targeted antibodies or ADCs.
E6 Participants who have received prior docetaxel therapy.
Models disagree, judged by models disagree, using F4
Writer said does not apply, checker said unknown. No prior systemic treatment means no prior docetaxel therapy.
E7 A history of other malignancies except:; Malignancy treated with curative intent and with no known active disease present for >=2 years before the first dose of study drug and felt to be at low risk for recurrence by investigator. Additionally, participants must not be receiving any ongoing anti-cancer therapy, including maintenance therapy, prior to randomization..; Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.; Adequately treated carcinoma in situ without current evidence of disease.
Unknown, judged by first model only
Answer cited no patient fact.
E8 A history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, evidence of active pneumonitis on screening chest computed tomography (CT) scan or prior pneumonectomy. A history of prior radiation pneumonitis in the radiation field (fibrosis) is not permitted.
Does not apply, judged by both models, using F9
No history of interstitial lung disease or other listed pulmonary conditions.
E9 Unresolved nor adverse event (AE) >= Grade 2 from prior anticancer therapy, except for alopecia or anemia. Participants with hormone deficiencies caused by prior anticancer therapy who are asymptomatic and on a stable dose of replacement hormone are eligible for study.
Does not apply, judged by both models, using F4
No prior anticancer therapy means no unresolved adverse events from such therapy.
E10 Major surgery within 21 days prior to randomization.
Unknown, judged by first model only
Answer cited no patient fact.
E11 Clinically significant condition(s) as listed in the protocol.
Unknown, judged by first model only
Specific protocol-defined clinically significant conditions are not detailed in the facts.
Not eligible Immunotherapy or Targeted Therapy With or Without Stereotactic Radiosurgery for Patients With Brain Metastases From Melanoma or Non-small Cell Lung Cancer I2 Not metI4 Not metI6 Not metI5 Models disagreeI16 Models disagreeI1 UnknownI3 UnknownI8 UnknownI9 UnknownI10 UnknownI11 UnknownI13 UnknownI17 UnknownI18 UnknownI19 UnknownI20 UnknownI21 UnknownI22 UnknownI23 UnknownI24 UnknownI25 UnknownI26 UnknownI27 UnknownI28 UnknownI29 At screeningI30 At screeningAGE-MIN MetI7 MetI12 MetI14 MetI15 Met Phase 3, ETOP IBCSG Partners Foundation. Nearest site: Zurich, Switzerland, 1 km away. 21 questions to clarify.
Ask before referring
- I1 Most important inclusion criteria:The specific text for this criterion is missing from the input.
- I3 Requirements for brain metastases:The specific text for this criterion is missing from the input.
- I5 Prior surgery (including biopsies, resection, and cyst aspiration) for brain metastases is allowed. Residual and measurable disease after surgery is not required, but surgery must have confirmed the diagnosis. An MRI performed within 72 hours post-surgery should be available.Writer said not met, checker said met. No brain metastases present, so surgery for them is not applicable.
- I8 Requirements for patients with melanoma:Criterion applies to melanoma; patient has NSCLC, but specific text is missing.
- I9 Prior treatment, including treatment with immune-checkpoint inhibitors is permitted, but brain metastases must be newly diagnosed and previously untreated (except for surgery).Criterion applies to melanoma; patient has NSCLC, but specific text is missing.
- I10 BRAF-mutation status, locally assessed, should be known (previous adjuvant BRAF-targeted therapy is allowed).Criterion applies to melanoma; patient has NSCLC, but specific text is missing.
- I11 Requirements for patients with NSCLC:The specific text for this criterion is missing from the input.
- I13 Known PD-L1 expression status (from primary tumour or from a metastatic lesion, including brain)PD-L1 expression status is not provided in the facts.
- I16 Karnofsky performance status of 60 or moreWriter said met, checker said unknown. ECOG 0 corresponds to a Karnofsky performance status of 100, which is >= 60.
- I17 Life expectancy >12 weeksLife expectancy is not explicitly stated in the facts.
- I18 Patients must be candidates for systemic treatment, within the defined cohorts (melanoma: cohorts 1a and 1b; NSCLC: cohorts 2a and 2b).Cohort assignment and candidacy for systemic treatment are not explicitly defined in facts.
- I19 Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test within 7 days before randomisation.Invalid answer 'does_not_apply'.
- I20 Written IC for study participation must be signed and dated by the patient and the investigator prior to any study-related intervention. Most important exclusion criteria:Informed consent status is not provided in the facts.
- I21 Confirmed or probable leptomeningeal metastases according to EANO ESMO criteriaPresence or absence of leptomeningeal metastases is not specified.
- I22 Symptomatic brain metastases at time of randomisation, e.g., neurological symptoms or signs that require more than a stable dose of 4 mg dexamethasone equivalent for more than one week.Invalid answer 'does_not_apply'.
- I23 Patients must be off steroids or on a stable dose of <=4 mg dexamethasone equivalent at randomisation.Current steroid usage status is not provided in the facts.
- I24 Patients experiencing seizures controlled by anti-epileptic drugs are eligible.Seizure history and control status are not provided in the facts.
- I25 Prior whole brain irradiation or focal radiation therapy to the brainHistory of prior brain radiation is not provided in the facts.
- I26 Prior systemic treatment for brain metastasesInvalid answer 'does_not_apply'.
- I27 Contra-indication for SRSContraindications for SRS are not assessed or listed in the facts.
- I28 Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.Investigator judgment on compliance is not provided in the facts.
What rules the patient out
- I2 Newly diagnosed, previously untreated (except for surgery, see below) asymptomatic or oligo-symptomatic brain metastases, e.g., controlled symptomatic seizure disorder. Note: patients with neurological symptoms or signs that require more than a stable dose of 4 mg dexamethasone equivalent for more than one week are not considered oligo-symptomatic.Patient has no brain metastases, so the requirement for newly diagnosed brain mets is not met.
- I4 Brain metastases must be previously untreated, except for surgery.Patient has no brain metastases to be previously untreated.
- I6 Number and size of metastases at diagnosis of brain metastases:; Maximum 1-10 brain metastases at screening; At least one brain metastasis must be of >=5 mm in diameter; In case of 1-4 brain metastases:; Longest diameter of largest brain metastasis must be <=30 mm; In case of 5-10 brain metastases:; Largest metastasis must be <=10 mL in volume and longest diameter must be <=30 mm; Maximum cumulative brain metastases volume must be <=30 mLPatient has zero brain metastases, failing the requirement of at least one.
Every criterion, as written in the registry
AGE-MIN Age at least 18 years
Met, judged by code, using F1
I1 Most important inclusion criteria:
Unknown, judged by first model only
The specific text for this criterion is missing from the input.
I2 Newly diagnosed, previously untreated (except for surgery, see below) asymptomatic or oligo-symptomatic brain metastases, e.g., controlled symptomatic seizure disorder. Note: patients with neurological symptoms or signs that require more than a stable dose of 4 mg dexamethasone equivalent for more than one week are not considered oligo-symptomatic.
Not met, judged by both models, using F5
Patient has no brain metastases, so the requirement for newly diagnosed brain mets is not met.
I3 Requirements for brain metastases:
Unknown, judged by first model only
The specific text for this criterion is missing from the input.
I4 Brain metastases must be previously untreated, except for surgery.
Not met, judged by both models, using F5
Patient has no brain metastases to be previously untreated.
I5 Prior surgery (including biopsies, resection, and cyst aspiration) for brain metastases is allowed. Residual and measurable disease after surgery is not required, but surgery must have confirmed the diagnosis. An MRI performed within 72 hours post-surgery should be available.
Models disagree, judged by models disagree, using F5
Writer said not met, checker said met. No brain metastases present, so surgery for them is not applicable.
I6 Number and size of metastases at diagnosis of brain metastases:; Maximum 1-10 brain metastases at screening; At least one brain metastasis must be of >=5 mm in diameter; In case of 1-4 brain metastases:; Longest diameter of largest brain metastasis must be <=30 mm; In case of 5-10 brain metastases:; Largest metastasis must be <=10 mL in volume and longest diameter must be <=30 mm; Maximum cumulative brain metastases volume must be <=30 mL
Not met, judged by both models, using F5
Patient has zero brain metastases, failing the requirement of at least one.
I7 Primary disease of histologically confirmed (from primary tumour or from a metastatic lesion, including in the brain) melanoma or NSCLC
Met, judged by both models, using F2
Patient has histologically confirmed non-small cell lung cancer.
I8 Requirements for patients with melanoma:
Unknown, judged by first model only
Criterion applies to melanoma; patient has NSCLC, but specific text is missing.
I9 Prior treatment, including treatment with immune-checkpoint inhibitors is permitted, but brain metastases must be newly diagnosed and previously untreated (except for surgery).
Unknown, judged by first model only
Criterion applies to melanoma; patient has NSCLC, but specific text is missing.
I10 BRAF-mutation status, locally assessed, should be known (previous adjuvant BRAF-targeted therapy is allowed).
Unknown, judged by first model only
Criterion applies to melanoma; patient has NSCLC, but specific text is missing.
I11 Requirements for patients with NSCLC:
Unknown, judged by first model only
The specific text for this criterion is missing from the input.
I12 Newly diagnosed, treatment-naïve (except for prior surgery) metastatic NSCLC, with or without a targetable oncogenic driver alteration.
Met, judged by both models, using F2 F4
Patient has newly diagnosed, treatment-naive metastatic NSCLC.
I13 Known PD-L1 expression status (from primary tumour or from a metastatic lesion, including brain)
Unknown, judged by first model only
PD-L1 expression status is not provided in the facts.
I14 Known driver mutation status (from primary tumour or from a metastatic lesion, including brain).
Met, judged by both models, using F3
Driver mutation status (EGFR exon 20 insertion) is known.
I15 Age of 18 years or older
Met, judged by both models, using F1
Patient is 54 years old, which is 18 or older.
I16 Karnofsky performance status of 60 or more
Models disagree, judged by models disagree, using F6
Writer said met, checker said unknown. ECOG 0 corresponds to a Karnofsky performance status of 100, which is >= 60.
I17 Life expectancy >12 weeks
Unknown, judged by first model only
Life expectancy is not explicitly stated in the facts.
I18 Patients must be candidates for systemic treatment, within the defined cohorts (melanoma: cohorts 1a and 1b; NSCLC: cohorts 2a and 2b).
Unknown, judged by first model only
Cohort assignment and candidacy for systemic treatment are not explicitly defined in facts.
I19 Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test within 7 days before randomisation.
Unknown, judged by first model only
Invalid answer 'does_not_apply'.
I20 Written IC for study participation must be signed and dated by the patient and the investigator prior to any study-related intervention. Most important exclusion criteria:
Unknown, judged by first model only
Informed consent status is not provided in the facts.
I21 Confirmed or probable leptomeningeal metastases according to EANO ESMO criteria
Unknown, judged by first model only
Presence or absence of leptomeningeal metastases is not specified.
I22 Symptomatic brain metastases at time of randomisation, e.g., neurological symptoms or signs that require more than a stable dose of 4 mg dexamethasone equivalent for more than one week.
Unknown, judged by first model only
Invalid answer 'does_not_apply'.
I23 Patients must be off steroids or on a stable dose of <=4 mg dexamethasone equivalent at randomisation.
Unknown, judged by first model only
Current steroid usage status is not provided in the facts.
I24 Patients experiencing seizures controlled by anti-epileptic drugs are eligible.
Unknown, judged by first model only
Seizure history and control status are not provided in the facts.
I25 Prior whole brain irradiation or focal radiation therapy to the brain
Unknown, judged by first model only
History of prior brain radiation is not provided in the facts.
I26 Prior systemic treatment for brain metastases
Unknown, judged by first model only
Invalid answer 'does_not_apply'.
I27 Contra-indication for SRS
Unknown, judged by first model only
Contraindications for SRS are not assessed or listed in the facts.
I28 Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
Unknown, judged by first model only
Investigator judgment on compliance is not provided in the facts.
I29 Women who are pregnant or in the period of lactation.
At screening, judged by code
Confirmed at screening (consent, pregnancy or protocol).
I30 Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study.
At screening, judged by code
Confirmed at screening (consent, pregnancy or protocol).
Not eligible A Clinical Trial to Test if an Investigational Combination Therapy With BNT326 and BNT327 is Safe and Potentially Beneficial for People With Advanced Non-small Cell Lung Cancer (NSCLC) I7 Not metI8 Not metI9 Not metI10 Not metI11 Not metI12 Not metI13 Models disagreeI14 Models disagreeI15 Models disagreeI16 Models disagreeI1 UnknownI17 UnknownI18 UnknownI19 UnknownI20 UnknownI21 UnknownI22 UnknownI23 UnknownI24 UnknownI26 UnknownI27 UnknownI28 UnknownI29 UnknownI30 UnknownI31 UnknownI25 At screeningAGE-MIN MetI2 MetI3 MetI4 MetI5 MetI6 Met Phase 1, Phase 2, BioNTech SE. Nearest site: Freiburg im Breisgau, Germany, 86 km away. 24 questions to clarify.
Ask before referring
- I1 Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified):General header criterion; specific applicability depends on other criteria.
- I13 Have received no systemic anti-cancer treatment in the advanced/metastatic setting. May have received neoadjuvant and/or adjuvant treatment if progression to advanced/metastatic disease occurred at least 6 months after completing such therapy and have not received treatment in the advanced/metastatic setting. Part 2b (Cohort C), 2L+, squamous or non-squamous NSCLC, AGA-negative or EGFR activating mutation, any PD-L1Writer said not met, checker said met. Patient has an actionable genomic alteration (EGFR exon 20 insertion).
- I14 for AGA-negative NSCLC only:; Have no actionable genomic alterations, such as EGFR mutations, ALK rearrangements, or other genomic alterations for which targeted molecular therapies are available.; Participants should have received 1 to 4 lines of systemic treatment, which can include anti-PD-1/PD-L1 therapy, chemotherapy, and/or anti-angiogenic agents.; Regimens used as neoadjuvant and/or adjuvant treatment may be considered as prior lines for advanced disease if relapse occurred within 6 months of the last dose.Writer said not met, checker said unknown. Patient has an actionable genomic alteration (EGFR exon 20 insertion).
- I15 for EGFR-sensitizing mutation NSCLC only:; Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del).; Have received 1 or 2 prior systemic therapies for advanced and/or metastatic disease with an approved EGFR TKI, which must include one third-generation anti-EGFR TKI.; Participants receiving an EGFR TKI at the time of signing informed consent may continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1.; Chemotherapy is permitted only if it was administered in combination with an EGFR TKI as part of a single line of therapy and as the initial (first line) treatment for advanced/metastatic disease.; May have received neoadjuvant and/or adjuvant treatment if progression to advanced/metastatic disease occurred at least 6 months after completing such therapy and have experienced disease progression on or after EGFR TKI treatment administered in the advanced/metastatic setting.; Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance. Part 2b (Cohort D1) 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 >=50% and Part 2b (Cohort D2) 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 <50%Writer said not met, checker said unknown. Patient has EGFR exon 20 insertion, not a sensitizing mutation, and no prior therapy.
- I16 Have no actionable genomic alterations, such as EGFR mutations (Cohort D1)/EGFR-sensitizing mutations (Cohort D2), ALK rearrangements, or other genomic alterations for which targeted molecular therapies are available.Writer said not met, checker said unknown. Patient has an actionable genomic alteration (EGFR exon 20 insertion).
- I17 Have not received prior systemic therapy for advanced and/or metastatic disease. May have received neoadjuvant and/or adjuvant treatment if progression to advanced/metastatic disease occurred at least 6 months after completing such therapy and have not received treatment in the advanced/metastatic setting. Key Exclusion Criteria (applicable to all participants and all parts):No facts provided regarding prior HER3 or topoisomerase I inhibitor treatment.
- I18 Had disease progression on or were intolerant to prior treatment with an agent targeting HER3 (including antibody, ADC, cell therapy, and other drugs) or with a topoisomerase I inhibitor payload (including topoisomerase I inhibitor-containing ADCs). Note: For Part 2a Cohort A, prior exposure to agents targeting HER3 or topoisomerase I inhibitor payload may be allowed on a case-by-case basis after discussion with and approval by the sponsor.No facts provided regarding uncontrolled concomitant illnesses.
- I19 Have an uncontrolled concomitant or intercurrent illness, that contra-indicates study participation, limits compliance with study procedures or substantially increases the risk of incurring AEs, including:; Bleeding diathesis or active hemorrhage; Clinically significant active infection, including respiratory viral infection; Child-Pugh class B or C cirrhosis; Known pulmonary disease with significant impact in lung function and/or with potential risk of severe infection; Oncologic emergencies or complications (e.g., malignant hypercalcemia, superior vena cava syndrome, carcinoid syndrome that is unstable and with available alternative therapies); Psychiatric or abuse condition; Infectious colitis Grade >=2 not resolved to Grade 1 within 72 h within the past 3 monthsNo facts provided regarding left ventricular ejection fraction.
- I20 Have left ventricular ejection fraction <50% by either echocardiography or multi-gated acquisition (scanning) within 28 days before randomization/enrollment.No facts provided regarding pleural, ascites, or pericardial effusion.
- I21 Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.Invalid answer 'does_not_apply'.
- I22 Have a history of (non-infectious) interstitial lung disease (ILD) /pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. Asymptomatic interstitial changes caused by previous radiation therapy, chemotherapy, or other factors such as smoking are acceptable.No facts provided regarding exposure to protocol-specific treatments.
- I23 Have had exposure to protocol-specific treatments with a washout period before randomization/enrollment.Invalid answer 'does_not_apply'.
- I24 Have clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.No facts provided regarding other investigational studies.
- I26 Are subject to exclusion periods from another investigational study.No facts provided regarding urine protein levels.
- I27 Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.No facts provided regarding immune-related adverse events.
- I28 Have urine protein >=2+ and 24-hour urine protein excretion >=1 g. If qualitative urine protein is <=1+, a 24-hour urine protein quantitative test is not required.No facts provided regarding risk of hemorrhage.
- I29 Have a history of Grade >=3 immune-related adverse events that led to treatment discontinuation of a prior checkpoint inhibitor.No facts provided regarding corneal disorders.
- I30 Have a significant risk of hemorrhage (per investigator clinical judgment) indicated by protocol defined criteria.No answer for this criterion.
- I31 Have active or chronic clinically significant corneal disorders or any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy. NOTE: Other protocol defined Inclusion/Exclusion criteria apply.No answer for this criterion.
- I7 for AGA-negative NSCLC only:; Have no actionable genomic alterations, such as EGFR mutations, anaplastic lymphoma kinase (ALK) gene rearrangements, or other genomic alterations for which targeted molecular therapies are available.; Have experienced relapse or progression during or after treatment with standard systemic therapy in the advanced/metastatic setting or discontinued from prior therapy due to intolerance.; Participants must have received 1 to 3 lines of systemic treatment in the metastatic setting, which can include anti-PD-1/PD-L1 therapy, chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently or sequentially. However, prior chemotherapy treatment must be limited to 2 lines or less.Patient has an EGFR mutation (AGA) and no prior systemic therapy.
- I8 for AGA-positive NSCLC only (excluding EGFR activating mutation):; Have documented positive test results for one or more actionable genomic alteration: EGFR (other than activating mutations), ALK, ROS proto-oncogene 1 (ROS1), gene encoding the hepatocyte growth factor receptor (MET), human gene that encodes a protein called B-Raf (BRAF), rearranged during transfection (RET), neurotrophic tropomyosin-receptor kinase (NTRK), human epidermal growth factor receptor 2 (HER2), Kirsten rat sarcoma virus (KRAS), or other genomic alteration with available targeted therapy.; Must have received at least one prior systemic therapy for advanced disease, which must have included targeted treatment for actionable genomic alterations, which include alterations such as EGFR (other than activating mutations), ALK, ROS1, MET, BRAF, RET, NTRK, HER2, KRAS, or other alterations for which targeted therapies are available as a part of local SoC.; Participants may have received between 1 to 3 lines of systemic treatment of anti-PD-1/PD-L1 therapy, chemotherapy, and/or anti-angiogenic agents. These treatments may be administered concurrently (including with tyrosine kinase inhibitor [TKI]) or sequentially. However, chemotherapy treatment must be limited to 2 lines or less.; Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.Patient has no prior systemic therapy, required for this cohort.
- I9 for AGA-positive NSCLC only (with EGFR activating mutation):; Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del).; Participants must have received one or two prior lines of systemic therapy for advanced and/or metastatic disease, which must include treatment with an approved EGFR TKI, with at least one being a third-generation EGFR TKI.; Participants receiving an EGFR TKI at the time of signing informed consent may continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1.; Chemotherapy is permitted only if it was administered in combination with an EGFR TKI as part of a single line of therapy and as the initial (first line) treatment for advanced/metastatic disease.; Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance. Part 2a (Cohort A), 2L+, squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1 (NOTE: regimens used as neoadjuvant and/or adjuvant treatment may be considered as prior lines for advanced disease if relapse occurred within 6 months of the last dose.)Patient has EGFR exon 20 insertion, not a sensitizing mutation, and no prior therapy.
- I10 for AGA-positive NSCLC only, excluding EGFR activating mutation:; Have documented positive test results for one or more actionable genomic alterations: EGFR (other than activating mutations), ALK, ROS1, MET, BRAF, RET, NTRK, HER2, KRAS, or other genomic alterations, with available targeted therapy.; May have received 1 to 4 lines of systemic treatment, of which one prior systemic therapy for advanced disease must have included targeted treatment for actionable genomic alterations, which include alterations such as EGFR (other than activating mutations), ALK, ROS1, MET, BRAF, RET, NTRK, HER2, KRAS, or other genomic alterations for which targeted therapies are available as part of local SoC.; Other therapies may include anti-PD-1/PD-L1 therapy, chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently/in combination (including with TKI) or sequentially. However, chemotherapy treatment must be limited to 2 lines or less.; Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.Patient has no prior systemic therapy, required for this cohort.
- I11 for AGA-positive NSCLC only, with EGFR activation mutation:; Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del).; Participants must have received one or two prior lines of systemic therapy for advanced and/or metastatic disease, which must include treatment with an approved EGFR TKI, with at least one being a third-generation EGFR TKI.; Participants receiving an EGFR TKI at the time of signing informed consent may continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1.; Chemotherapy is permitted only if it was administered in combination with an EGFR TKI as part of a single line of therapy and as the initial (first line) treatment for advanced/metastatic disease.; Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance. Part 2a (Cohort B), 1L, squamous or non-squamous NSCLC, AGA-negative, any PD-L1Patient has EGFR exon 20 insertion, not a sensitizing mutation, and no prior therapy.
What rules the patient out
- I12 Have no actionable genomic alterations, such as EGFR mutations, ALK rearrangements, or other genomic alterations for which targeted molecular therapies are available.Patient has an actionable genomic alteration (EGFR exon 20 insertion).
Every criterion, as written in the registry
AGE-MIN Age at least 18 years
Met, judged by code, using F1
I1 Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified):
Unknown, judged by first model only
General header criterion; specific applicability depends on other criteria.
I2 Aged >=18 years at the time of giving informed consent. Local laws will be followed if the age of consent is older.
Met, judged by both models, using F1
Patient is 54 years old, which is >= 18.
I3 Have measurable disease defined by RECIST v1.1.
Met, judged by both models, using F7
Patient has measurable disease defined by RECIST v1.1.
I4 Have Eastern Cooperative Oncology Group performance status of 0 or 1.
Met, judged by both models, using F6
ECOG performance status is 0, which is 0 or 1.
I5 Have adequate organ and bone marrow function within 7 days before randomization/enrollment as defined in the protocol.
Met, judged by both models, using F8
Lab values show adequate organ and bone marrow function.
I6 Have advanced (i.e., metastatic or locally recurrent where local therapy with curative intent is not possible) non-squamous or squamous NSCLC. Cohort-specific inclusion criteria Part 1, 2L+, squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1 (NOTE: regimens used as neoadjuvant and/or adjuvant treatment may be considered as prior lines for advanced disease if relapse occurred within 6 months of the last dose.)
Met, judged by both models, using F2
Patient has advanced non-squamous NSCLC.
I7 for AGA-negative NSCLC only:; Have no actionable genomic alterations, such as EGFR mutations, anaplastic lymphoma kinase (ALK) gene rearrangements, or other genomic alterations for which targeted molecular therapies are available.; Have experienced relapse or progression during or after treatment with standard systemic therapy in the advanced/metastatic setting or discontinued from prior therapy due to intolerance.; Participants must have received 1 to 3 lines of systemic treatment in the metastatic setting, which can include anti-PD-1/PD-L1 therapy, chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently or sequentially. However, prior chemotherapy treatment must be limited to 2 lines or less.
Not met, judged by both models, using F3 F4
Patient has an EGFR mutation (AGA) and no prior systemic therapy.
I8 for AGA-positive NSCLC only (excluding EGFR activating mutation):; Have documented positive test results for one or more actionable genomic alteration: EGFR (other than activating mutations), ALK, ROS proto-oncogene 1 (ROS1), gene encoding the hepatocyte growth factor receptor (MET), human gene that encodes a protein called B-Raf (BRAF), rearranged during transfection (RET), neurotrophic tropomyosin-receptor kinase (NTRK), human epidermal growth factor receptor 2 (HER2), Kirsten rat sarcoma virus (KRAS), or other genomic alteration with available targeted therapy.; Must have received at least one prior systemic therapy for advanced disease, which must have included targeted treatment for actionable genomic alterations, which include alterations such as EGFR (other than activating mutations), ALK, ROS1, MET, BRAF, RET, NTRK, HER2, KRAS, or other alterations for which targeted therapies are available as a part of local SoC.; Participants may have received between 1 to 3 lines of systemic treatment of anti-PD-1/PD-L1 therapy, chemotherapy, and/or anti-angiogenic agents. These treatments may be administered concurrently (including with tyrosine kinase inhibitor [TKI]) or sequentially. However, chemotherapy treatment must be limited to 2 lines or less.; Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.
Not met, judged by both models, using F3 F4
Patient has no prior systemic therapy, required for this cohort.
I9 for AGA-positive NSCLC only (with EGFR activating mutation):; Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del).; Participants must have received one or two prior lines of systemic therapy for advanced and/or metastatic disease, which must include treatment with an approved EGFR TKI, with at least one being a third-generation EGFR TKI.; Participants receiving an EGFR TKI at the time of signing informed consent may continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1.; Chemotherapy is permitted only if it was administered in combination with an EGFR TKI as part of a single line of therapy and as the initial (first line) treatment for advanced/metastatic disease.; Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance. Part 2a (Cohort A), 2L+, squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1 (NOTE: regimens used as neoadjuvant and/or adjuvant treatment may be considered as prior lines for advanced disease if relapse occurred within 6 months of the last dose.)
Not met, judged by both models, using F3 F4
Patient has EGFR exon 20 insertion, not a sensitizing mutation, and no prior therapy.
I10 for AGA-positive NSCLC only, excluding EGFR activating mutation:; Have documented positive test results for one or more actionable genomic alterations: EGFR (other than activating mutations), ALK, ROS1, MET, BRAF, RET, NTRK, HER2, KRAS, or other genomic alterations, with available targeted therapy.; May have received 1 to 4 lines of systemic treatment, of which one prior systemic therapy for advanced disease must have included targeted treatment for actionable genomic alterations, which include alterations such as EGFR (other than activating mutations), ALK, ROS1, MET, BRAF, RET, NTRK, HER2, KRAS, or other genomic alterations for which targeted therapies are available as part of local SoC.; Other therapies may include anti-PD-1/PD-L1 therapy, chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently/in combination (including with TKI) or sequentially. However, chemotherapy treatment must be limited to 2 lines or less.; Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.
Not met, judged by both models, using F3 F4
Patient has no prior systemic therapy, required for this cohort.
I11 for AGA-positive NSCLC only, with EGFR activation mutation:; Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del).; Participants must have received one or two prior lines of systemic therapy for advanced and/or metastatic disease, which must include treatment with an approved EGFR TKI, with at least one being a third-generation EGFR TKI.; Participants receiving an EGFR TKI at the time of signing informed consent may continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1.; Chemotherapy is permitted only if it was administered in combination with an EGFR TKI as part of a single line of therapy and as the initial (first line) treatment for advanced/metastatic disease.; Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance. Part 2a (Cohort B), 1L, squamous or non-squamous NSCLC, AGA-negative, any PD-L1
Not met, judged by both models, using F3 F4
Patient has EGFR exon 20 insertion, not a sensitizing mutation, and no prior therapy.
I12 Have no actionable genomic alterations, such as EGFR mutations, ALK rearrangements, or other genomic alterations for which targeted molecular therapies are available.
Not met, judged by both models, using F3
Patient has an actionable genomic alteration (EGFR exon 20 insertion).
I13 Have received no systemic anti-cancer treatment in the advanced/metastatic setting. May have received neoadjuvant and/or adjuvant treatment if progression to advanced/metastatic disease occurred at least 6 months after completing such therapy and have not received treatment in the advanced/metastatic setting. Part 2b (Cohort C), 2L+, squamous or non-squamous NSCLC, AGA-negative or EGFR activating mutation, any PD-L1
Models disagree, judged by models disagree, using F3
Writer said not met, checker said met. Patient has an actionable genomic alteration (EGFR exon 20 insertion).
I14 for AGA-negative NSCLC only:; Have no actionable genomic alterations, such as EGFR mutations, ALK rearrangements, or other genomic alterations for which targeted molecular therapies are available.; Participants should have received 1 to 4 lines of systemic treatment, which can include anti-PD-1/PD-L1 therapy, chemotherapy, and/or anti-angiogenic agents.; Regimens used as neoadjuvant and/or adjuvant treatment may be considered as prior lines for advanced disease if relapse occurred within 6 months of the last dose.
Models disagree, judged by models disagree, using F3
Writer said not met, checker said unknown. Patient has an actionable genomic alteration (EGFR exon 20 insertion).
I15 for EGFR-sensitizing mutation NSCLC only:; Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del).; Have received 1 or 2 prior systemic therapies for advanced and/or metastatic disease with an approved EGFR TKI, which must include one third-generation anti-EGFR TKI.; Participants receiving an EGFR TKI at the time of signing informed consent may continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1.; Chemotherapy is permitted only if it was administered in combination with an EGFR TKI as part of a single line of therapy and as the initial (first line) treatment for advanced/metastatic disease.; May have received neoadjuvant and/or adjuvant treatment if progression to advanced/metastatic disease occurred at least 6 months after completing such therapy and have experienced disease progression on or after EGFR TKI treatment administered in the advanced/metastatic setting.; Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance. Part 2b (Cohort D1) 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 >=50% and Part 2b (Cohort D2) 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 <50%
Models disagree, judged by models disagree, using F3 F4
Writer said not met, checker said unknown. Patient has EGFR exon 20 insertion, not a sensitizing mutation, and no prior therapy.
I16 Have no actionable genomic alterations, such as EGFR mutations (Cohort D1)/EGFR-sensitizing mutations (Cohort D2), ALK rearrangements, or other genomic alterations for which targeted molecular therapies are available.
Models disagree, judged by models disagree, using F3
Writer said not met, checker said unknown. Patient has an actionable genomic alteration (EGFR exon 20 insertion).
I17 Have not received prior systemic therapy for advanced and/or metastatic disease. May have received neoadjuvant and/or adjuvant treatment if progression to advanced/metastatic disease occurred at least 6 months after completing such therapy and have not received treatment in the advanced/metastatic setting. Key Exclusion Criteria (applicable to all participants and all parts):
Unknown, judged by first model only
No facts provided regarding prior HER3 or topoisomerase I inhibitor treatment.
I18 Had disease progression on or were intolerant to prior treatment with an agent targeting HER3 (including antibody, ADC, cell therapy, and other drugs) or with a topoisomerase I inhibitor payload (including topoisomerase I inhibitor-containing ADCs). Note: For Part 2a Cohort A, prior exposure to agents targeting HER3 or topoisomerase I inhibitor payload may be allowed on a case-by-case basis after discussion with and approval by the sponsor.
Unknown, judged by first model only
No facts provided regarding uncontrolled concomitant illnesses.
I19 Have an uncontrolled concomitant or intercurrent illness, that contra-indicates study participation, limits compliance with study procedures or substantially increases the risk of incurring AEs, including:; Bleeding diathesis or active hemorrhage; Clinically significant active infection, including respiratory viral infection; Child-Pugh class B or C cirrhosis; Known pulmonary disease with significant impact in lung function and/or with potential risk of severe infection; Oncologic emergencies or complications (e.g., malignant hypercalcemia, superior vena cava syndrome, carcinoid syndrome that is unstable and with available alternative therapies); Psychiatric or abuse condition; Infectious colitis Grade >=2 not resolved to Grade 1 within 72 h within the past 3 months
Unknown, judged by first model only
No facts provided regarding left ventricular ejection fraction.
I20 Have left ventricular ejection fraction <50% by either echocardiography or multi-gated acquisition (scanning) within 28 days before randomization/enrollment.
Unknown, judged by first model only
No facts provided regarding pleural, ascites, or pericardial effusion.
I21 Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.
Unknown, judged by first model only
Invalid answer 'does_not_apply'.
I22 Have a history of (non-infectious) interstitial lung disease (ILD) /pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. Asymptomatic interstitial changes caused by previous radiation therapy, chemotherapy, or other factors such as smoking are acceptable.
Unknown, judged by first model only
No facts provided regarding exposure to protocol-specific treatments.
I23 Have had exposure to protocol-specific treatments with a washout period before randomization/enrollment.
Unknown, judged by first model only
Invalid answer 'does_not_apply'.
I24 Have clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
Unknown, judged by first model only
No facts provided regarding other investigational studies.
I25 Are participants of childbearing potential who are pregnant or breastfeeding or are planning pregnancy within the time specified in the protocol or are potentially fertile males, who are planning to father children during the study or within the time specified in the protocol.
At screening, judged by code
Confirmed at screening (consent, pregnancy or protocol).
I26 Are subject to exclusion periods from another investigational study.
Unknown, judged by first model only
No facts provided regarding urine protein levels.
I27 Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
Unknown, judged by first model only
No facts provided regarding immune-related adverse events.
I28 Have urine protein >=2+ and 24-hour urine protein excretion >=1 g. If qualitative urine protein is <=1+, a 24-hour urine protein quantitative test is not required.
Unknown, judged by first model only
No facts provided regarding risk of hemorrhage.
I29 Have a history of Grade >=3 immune-related adverse events that led to treatment discontinuation of a prior checkpoint inhibitor.
Unknown, judged by first model only
No facts provided regarding corneal disorders.
I30 Have a significant risk of hemorrhage (per investigator clinical judgment) indicated by protocol defined criteria.
Unknown, judged by first model only
No answer for this criterion.
I31 Have active or chronic clinically significant corneal disorders or any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy. NOTE: Other protocol defined Inclusion/Exclusion criteria apply.
Unknown, judged by first model only
No answer for this criterion.