Possible 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) E3 Models disagreeE4 At screeningAGE-MIN MetI1 MetI2 MetI3 MetI4 MetE1 Does not applyE2 Does not apply Phase 2, Phase 3, Bristol-Myers Squibb. Nearest site: Baden, Switzerland, 55 km away. 1 question to clarify.
Ask before referring
- E3 Poorly controlled systemic medical conditions.Writer said does not apply, checker said unknown. ECOG 1, no active infections, cardiac issues, or ILD.
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 metastatic and not curable.
I2 Documented evidence of EGFR mutation (exon 19 deletion, L858R mutation).
Met, judged by both models, using F3
EGFR exon 19 deletion is a documented qualifying mutation.
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.
Met, judged by both models, using F4 F5
Progression on osimertinib, a 3rd-gen EGFR-TKI, as most recent therapy.
I4 Eligible to receive a platinum-based doublet chemotherapy regimen (either cisplatin or carboplatin in combination with pemetrexed).
Met, judged by both models, using F12
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 F12
Lab values show adequate organ function and bone marrow reserve.
E2 Leptomeningeal metastases or spinal cord compression.
Does not apply, judged by both models, using F9
No leptomeningeal disease or spinal cord compression present.
E3 Poorly controlled systemic medical conditions.
Models disagree, judged by models disagree, using F10 F13 F14 F15
Writer said does not apply, checker said unknown. ECOG 1, no active infections, cardiac issues, or ILD.
E4 Other protocol-defined inclusion/exclusion criteria apply.
At screening, judged by code
Confirmed at screening (consent, pregnancy or protocol).
Possible A Study of Clinical Outcomes in Participants With EGFR Mutated Advanced Non-Small Cell Lung Cancer (NSCLC) in a Real-World Setting I1 Models disagreeE2 Models disagreeI3 UnknownI4 UnknownI2 At screeningAGE-MIN MetE1 Does not applyE3 Does not applyE4 Does not apply Phase not given, Janssen Research & Development, LLC. Nearest site: Konstanz, Germany, 120 km away. 4 questions to clarify.
Ask before referring
- 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 amivantamabWriter said met, checker said unknown. Patient has confirmed EGFR exon 19 deletion in NSCLC.
- 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 collectionFacts do not specify if initiation is planned within 4 weeks.
- 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 studyFacts do not confirm decision was made prior to enrollment.
- E2 Participant has received prior treatment with amivantamab in a clinical trial or for compassionate useWriter said does not apply, checker said unknown. No history of amivantamab use in trials or compassionate use.
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
Models disagree, judged by models disagree, using F2 F3
Writer said met, checker said unknown. Patient has confirmed EGFR exon 19 deletion in NSCLC.
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
Facts do not specify if initiation is planned within 4 weeks.
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
Facts do not confirm 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 F5 F7
No active systemic anticancer treatment currently; prior osimertinib is not active.
E2 Participant has received prior treatment with amivantamab in a clinical trial or for compassionate use
Models disagree, judged by models disagree, using F4 F7
Writer said does not apply, checker said unknown. No history of amivantamab use in trials or compassionate use.
E3 Participants who are not receiving amivantamab but are being treated with a biosimilar or a non-original biologic agent
Does not apply, judged by both models, using F4 F7
No current treatment with biosimilar or non-original biologic agent.
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)
Does not apply, judged by both models, using F12 F13 F14 F15
No listed contraindications; labs and history are within acceptable limits.
Possible 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) I5 Models disagreeI6 Models disagreeI7 Models disagreeI8 Models disagreeI9 Models disagreeI10 Models disagreeI11 Models disagreeI12 Models disagreeI13 Models disagreeI14 Models disagreeI15 Models disagreeI16 Models disagreeI17 Models disagreeI1 UnknownI18 UnknownI19 UnknownI20 UnknownI21 UnknownI22 UnknownI23 UnknownI24 UnknownI26 UnknownI27 UnknownI28 UnknownI29 UnknownI30 UnknownI31 UnknownI25 At screeningAGE-MIN MetI2 MetI3 MetI4 Met Phase 1, Phase 2, BioNTech SE. Nearest site: Freiburg im Breisgau, Germany, 52 km away. 27 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.
- I5 Have adequate organ and bone marrow function within 7 days before randomization/enrollment as defined in the protocol.Writer said met, checker said unknown. 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.)Writer said met, checker said unknown. Patient has stage IV non-squamous NSCLC, which is advanced.
- 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.Writer said not met, checker said unknown. Patient has an EGFR mutation, so they are not AGA-negative.
- 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.Writer said not met, checker said unknown. Criterion excludes EGFR activating mutations; patient has one.
- 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.)Writer said not met, checker said unknown. Patient received only 1 prior line; criterion requires 1 or 2 prior lines.
- 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.Writer said not met, checker said unknown. Criterion excludes EGFR activating mutations; patient has one.
- 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-L1Writer said not met, checker said unknown. Patient received only 1 prior line; criterion requires 1 or 2 prior lines.
- I12 Have no actionable genomic alterations, such as EGFR mutations, 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 mutation).
- 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 unknown. Patient received prior systemic treatment in the advanced setting.
- 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 mutation).
- 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 received only 1 prior line; criterion requires 1 or 2 prior lines.
- 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 mutation).
- 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):Writer said not met, checker said unknown. Patient received prior systemic therapy for advanced disease.
- 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.Facts do not specify prior HER3 or topoisomerase I inhibitor exposure.
- 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 monthsFacts do not provide sufficient detail to rule out all listed conditions.
- I20 Have left ventricular ejection fraction <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 information on 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.Invalid answer 'does_not_apply'.
- I23 Have had exposure to protocol-specific treatments with a washout period before randomization/enrollment.No information on prior protocol-specific treatments or washout.
- I24 Have clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.Invalid answer 'does_not_apply'.
- I26 Are subject to exclusion periods from another investigational study.No information on other investigational studies.
- I27 Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.No information on small bowel obstruction history.
- 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 urine protein data provided.
- I29 Have a history of Grade >=3 immune-related adverse events that led to treatment discontinuation of a prior checkpoint inhibitor.Invalid answer 'does_not_apply'.
- I30 Have a significant risk of hemorrhage (per investigator clinical judgment) indicated by protocol defined criteria.No specific hemorrhage risk assessment provided.
- 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 corneal disorder history provided.
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 61 years old, which is >= 18.
I3 Have measurable disease defined by RECIST v1.1.
Met, judged by both models, using F11
Patient has a measurable lesion defined by RECIST 1.1.
I4 Have Eastern Cooperative Oncology Group performance status of 0 or 1.
Met, judged by both models, using F10
ECOG performance status is 1, which is 0 or 1.
I5 Have adequate organ and bone marrow function within 7 days before randomization/enrollment as defined in the protocol.
Models disagree, judged by models disagree, using F12
Writer said met, checker said unknown. 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.)
Models disagree, judged by models disagree, using F2
Writer said met, checker said unknown. Patient has stage IV non-squamous NSCLC, which is advanced.
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.
Models disagree, judged by models disagree, using F3
Writer said not met, checker said unknown. Patient has an EGFR mutation, so they are not AGA-negative.
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.
Models disagree, judged by models disagree, using F3
Writer said not met, checker said unknown. Criterion excludes EGFR activating mutations; patient has one.
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.)
Models disagree, judged by models disagree, using F4
Writer said not met, checker said unknown. Patient received only 1 prior line; criterion requires 1 or 2 prior lines.
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.
Models disagree, judged by models disagree, using F3
Writer said not met, checker said unknown. Criterion excludes EGFR activating mutations; patient has one.
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
Models disagree, judged by models disagree, using F4
Writer said not met, checker said unknown. Patient received only 1 prior line; criterion requires 1 or 2 prior lines.
I12 Have no actionable genomic alterations, such as EGFR mutations, 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 mutation).
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 F4
Writer said not met, checker said unknown. Patient received prior systemic treatment in the advanced setting.
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 mutation).
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 F4
Writer said not met, checker said unknown. Patient received only 1 prior line; criterion requires 1 or 2 prior lines.
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 mutation).
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):
Models disagree, judged by models disagree, using F4
Writer said not met, checker said unknown. Patient received prior systemic therapy for advanced disease.
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
Facts do not specify prior HER3 or topoisomerase I inhibitor exposure.
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
Facts do not provide sufficient detail to rule out all listed conditions.
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 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 information on 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
Invalid answer 'does_not_apply'.
I23 Have had exposure to protocol-specific treatments with a washout period before randomization/enrollment.
Unknown, judged by first model only
No information on prior protocol-specific treatments or washout.
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
Invalid answer 'does_not_apply'.
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 information on other investigational studies.
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 information on small bowel obstruction history.
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 urine protein data provided.
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
Invalid answer 'does_not_apply'.
I30 Have a significant risk of hemorrhage (per investigator clinical judgment) indicated by protocol defined criteria.
Unknown, judged by first model only
No specific hemorrhage risk assessment provided.
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 corneal disorder history provided.
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) I4 Not metE2 Applies, excludesI3 Models disagreeE1 Models disagreeE3 Models disagreeE4 UnknownE5 UnknownAGE-MIN MetI1 MetI2 MetI5 MetE6 Does not apply Phase 3, Bayer. Nearest site: Fribourg, Switzerland, 90 km away. 5 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 and MET alterations, but no documented HER2 TKD mutation.
- 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.Writer said does not apply, checker said unknown. No history of prior malignancy other than the current NSCLC is listed.
- 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.Writer said does not apply, checker said unknown. Patient is not on chronic systemic corticosteroids.
- E4 Pre-existing peripheral neuropathy that is Grade >=2 by CTCAE (v5.0).No information provided regarding peripheral neuropathy status.
- E5 History of severe hypersensitivity reaction to treatment with a monoclonal antibody.No information provided regarding hypersensitivity reactions to monoclonal antibodies.
What rules the patient out
- 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.Patient received prior systemic therapy (osimertinib) for metastatic disease.
- E2 Tumors with targetable alterations with approved available therapy, with the exception of HER2 mutation in the TKD.EGFR exon 19 deletion is a targetable alteration with approved therapy.
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 61 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 F6
Writer said not met, checker said unknown. Patient has EGFR and MET alterations, but no documented 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.
Not met, judged by both models, using F4
Patient received prior systemic therapy (osimertinib) for metastatic disease.
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.
Met, judged by both models, using F12 F15
Labs and cardiac status support eligibility for chemo and pembrolizumab.
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.
Models disagree, judged by models disagree, using F2
Writer said does not apply, checker said unknown. No history of prior malignancy other than the current NSCLC is listed.
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 exon 19 deletion is a targetable alteration with approved therapy.
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.
Models disagree, judged by models disagree, using F8
Writer said does not apply, checker said unknown. Patient is not on chronic systemic corticosteroids.
E4 Pre-existing peripheral neuropathy that is Grade >=2 by CTCAE (v5.0).
Unknown, judged by first model only
No information provided regarding peripheral neuropathy status.
E5 History of severe hypersensitivity reaction to treatment with a monoclonal antibody.
Unknown, judged by first model only
No information provided regarding hypersensitivity reactions to monoclonal antibodies.
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.
Does not apply, judged by both models, using F8
Brain radiotherapy was 8 months ago, exceeding the 21-day window.
Not eligible Phase III, Open-label Study of First-line Osimertinib With or Without Datopotamab Deruxtecan for EGFRm Locally Advanced or Metastatic Non-small Cell Lung Cancer I4 Not metE1 Models disagreeE3 Models disagreeE8 Models disagreeI6 UnknownE2 UnknownE5 UnknownAGE-MIN MetI1 MetI2 MetI3 MetI5 MetI7 MetI8 MetI9 MetE4 Does not applyE6 Does not applyE7 Does not apply Phase 3, AstraZeneca. Nearest site: Strasbourg, France, 114 km away. 6 questions to clarify.
Ask before referring
- I6 For participants enrolled in randomisation period, mandatory provision of an unstained, archival tumour tissue sample in a quantity sufficient to allow for central confirmation of the EGFR mutation status.Facts do not state if an archival tissue sample is available for central confirmation.
- E1 As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases, history of allogenic organ transplant which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.Writer said does not apply, checker said unknown. No evidence of severe uncontrolled systemic diseases or conditions jeopardizing compliance.
- E2 Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of osimertinib.Answer cited no patient fact.
- E3 History of another primary malignancy.Writer said does not apply, checker said unknown. Only NSCLC is listed; no history of other primary malignancies mentioned.
- E5 Clinically significant corneal disease.Answer cited no patient fact.
- E8 Has clinically severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.Writer said does not apply, checker said unknown. No history of ILD or pneumonitis suggests no severe pulmonary compromise from these.
What rules the patient out
- I4 Participants must not have received prior EGFR TKIs or other systemic therapy for Stage IIIB, IIIC or IV NSCLC.Patient received osimertinib, an EGFR TKI, as first-line treatment.
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. Type of Participant and Disease Characteristics
Met, judged by both models, using F1
Patient is 61 years old, which is greater than or equal to 18.
I2 Histologically or cytologically documented nonsquamous NSCLC. NSCLC of mixed histology is allowed if adenocarcinoma is the predominant histology. Mixed small-cell lung cancer and NSCLC histology, and sarcomatoid variant of NSCLC is ineligible.
Met, judged by both models, using F2
Diagnosis is non-small cell lung cancer, adenocarcinoma (non-squamous).
I3 Stage IIIB or IIIC or Stage IV metastatic NSCLC or recurrent NSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative surgery or definitive chemoradiation at the time of randomisation.
Met, judged by both models, using F2
Patient has Stage IV metastatic NSCLC.
I4 Participants must not have received prior EGFR TKIs or other systemic therapy for Stage IIIB, IIIC or IV NSCLC.
Not met, judged by both models, using F4
Patient received osimertinib, an EGFR TKI, as first-line treatment.
I5 The tumour harbors at least 1 of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del or L858R), either alone or in combination with other genomic alterations, which may include EGFR T790M, assessed by a CLIA-certified (US sites) or an accredited (outside of the US) local laboratory or by central prospective tissue testing.
Met, judged by both models, using F3
EGFR exon 19 deletion detected, which is a common sensitive mutation.
I6 For participants enrolled in randomisation period, mandatory provision of an unstained, archival tumour tissue sample in a quantity sufficient to allow for central confirmation of the EGFR mutation status.
Unknown, judged by first model only
Facts do not state if an archival tissue sample is available for central confirmation.
I7 WHO performance status of 0 or 1.
Met, judged by both models, using F10
ECOG performance status is 1, which is within the required 0 or 1 range.
I8 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.
Met, judged by both models, using F8 F11
Right lower lobe mass is 32mm (>=10mm) and not previously irradiated.
I9 Adequate bone marrow reserve and organ function before the first dose of study intervention.
Met, judged by both models, using F12
Lab values for blood counts, liver, and kidney function are within adequate ranges.
E1 As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases, history of allogenic organ transplant which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.
Models disagree, judged by models disagree, using F1 F2 F10 F12 F15
Writer said does not apply, checker said unknown. No evidence of severe uncontrolled systemic diseases or conditions jeopardizing compliance.
E2 Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of osimertinib.
Unknown, judged by first model only
Answer cited no patient fact.
E3 History of another primary malignancy.
Models disagree, judged by models disagree, using F2
Writer said does not apply, checker said unknown. Only NSCLC is listed; no history of other primary malignancies mentioned.
E4 Spinal cord compression and/or unstable brain metastases.
Does not apply, judged by both models, using F8 F9
No spinal cord compression and brain metastases are stable.
E5 Clinically significant corneal disease.
Unknown, judged by first model only
Answer cited no patient fact.
E6 Has active or uncontrolled hepatitis B or C virus infection, as defined by Protocol.
Does not apply, judged by both models, using F14
No active hepatitis B, C, or HIV infection.
E7 Past medical history of ILD/penumonitis, including radiation pneumonitis (apart from radiation pneumonitis that did not require steroids), or drug-induced ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
Does not apply, judged by both models, using F13
No history of interstitial lung disease or pneumonitis.
E8 Has clinically severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.
Models disagree, judged by models disagree, using F13
Writer said does not apply, checker said unknown. No history of ILD or pneumonitis suggests no severe pulmonary compromise from these.
Not eligible A Global Phase III Study of Rilvegostomig or Pembrolizumab Plus Chemotherapy for First-Line Treatment of Locally Advanced or Metastatic Non-Squamous NSCLC I3 Not metE3 Models disagreeI4 UnknownI5 UnknownE6 UnknownE7 UnknownE9 UnknownAGE-MIN MetI1 MetI2 MetI6 MetI7 MetE1 Does not applyE2 Does not applyE4 Does not applyE5 Does not applyE8 Does not apply Phase 3, AstraZeneca. Nearest site: Strasbourg, France, 114 km away. 6 questions to clarify.
Ask before referring
- 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.Facts do not specify status of other actionable driver oncogenes.
- I5 Provision of acceptable tumor sample, to confirm tumor PD-L1 expression TC >= 1%.PD-L1 expression status is not provided in the facts.
- 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.Writer said does not apply, checker said applies. Progression occurred 24 months after starting osimertinib, which is >12 months.
- 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.
- E7 Active or prior documented autoimmune or inflammatory disorders requiring chronic systemic treatment with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs.No information provided regarding autoimmune or inflammatory disorders.
- E9 Active tuberculosis infection.No information provided regarding tuberculosis infection.
What rules the patient out
- 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.Patient has EGFR exon 19 deletion, which is a sensitizing mutation.
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 (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.
Not met, judged by both models, using F3
Patient has EGFR exon 19 deletion, which is a sensitizing mutation.
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
Facts do not specify status of other actionable driver oncogenes.
I5 Provision of acceptable tumor sample, to confirm tumor PD-L1 expression TC >= 1%.
Unknown, judged by first model only
PD-L1 expression status is not provided in the 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.
Met, judged by both models, using F8 F11
Right lower lobe mass is 32mm, measurable, and not previously irradiated.
I7 Adequate organ and bone marrow function
Met, judged by both models, using F12
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
Histology is adenocarcinoma, not small cell or neuroendocrine.
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 F8
Brain metastases are asymptomatic, stable, no steroids, and >2 weeks post-therapy.
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.
Models disagree, judged by models disagree, using F4 F5
Writer said does not apply, checker said applies. Progression occurred 24 months after starting osimertinib, which is >12 months.
E4 Any prior exposure to an anti-TIGIT therapy or any other anticancer therapy targeting immune-regulatory receptors or mechanisms.
Does not apply, judged by both models, using F4 F7
No prior exposure to anti-TIGIT or other immune-regulatory therapies.
E5 Any prior treatment with an anti-PD-1 or anti-PD-L1 agent.
Does not apply, judged by both models, using F7
No 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.
Unknown, judged by first model only
No information provided regarding autoimmune or inflammatory disorders.
E8 Active primary immunodeficiency/active infectious disease(s).
Does not apply, judged by both models, using F14
No active hepatitis B, C, or HIV infection listed.
E9 Active tuberculosis infection.
Unknown, judged by first model only
No information provided regarding tuberculosis infection.
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 metI7 Not metI3 Models disagreeI11 Models disagreeE1 Models disagreeE2 Models disagreeI6 UnknownI8 UnknownI9 UnknownI10 UnknownI12 UnknownI1 At screeningE4 At screeningAGE-MIN MetI2 MetI5 MetE3 Does not applyE5 Does not apply n/a, Intergroupe Francophone de Cancerologie Thoracique. Nearest site: Colmar, France, 61 km away. 9 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, implying no pre-surgical evaluation for resection was performed.
- I6 Archival tumour tissue FFPE blocks from surgery available for centrally molecular analyses.No facts mention availability of archival surgical tissue blocks.
- 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 facts describe the patient's follow-up schedule or institution adherence.
- 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.Writer said met, checker said not met. Patient is post-menopausal, so childbearing potential criteria do 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.Invalid answer 'does_not_apply'.
- 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 other cancers is mentioned; current cancer is the primary diagnosis.
- E2 Neoadjuvant anti-cancer treatment (osimertinib and/or chemotherapy or other anti-cancer treatment).Writer said applies, checker said does not apply. Patient received osimertinib as first-line treatment, which is an anti-cancer treatment.
What rules the patient out
- I4 Histologically complete anatomical resection (R0) of stage pIB-IIIA (pTNM 8th edition) NSCLC.Patient has stage IV NSCLC, not stage pIB-IIIA, and no resection occurred.
- 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.Patient has stage IV disease and received first-line osimertinib, not adjuvant therapy.
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 61 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, implying no pre-surgical evaluation for resection was performed.
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 NSCLC, not stage pIB-IIIA, and no resection occurred.
I5 Presence of a common EGFR mutation (Del19 or L858R).
Met, judged by both models, using F3
EGFR exon 19 deletion is a common EGFR mutation.
I6 Archival tumour tissue FFPE blocks from surgery available for centrally molecular analyses.
Unknown, judged by first model only
No facts mention availability of archival surgical 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.
Not met, judged by both models, using F2 F4
Patient has stage IV disease and received first-line osimertinib, not adjuvant therapy.
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 facts describe the patient's follow-up schedule or institution adherence.
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.
Models disagree, judged by models disagree, using F1 F16
Writer said met, checker said not met. Patient is post-menopausal, so childbearing potential criteria do 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
Invalid answer 'does_not_apply'.
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 other cancers is mentioned; current cancer is the primary diagnosis.
E2 Neoadjuvant anti-cancer treatment (osimertinib and/or chemotherapy or other anti-cancer treatment).
Models disagree, judged by models disagree, using F4
Writer said applies, checker said does not apply. Patient received osimertinib as first-line treatment, which is an anti-cancer treatment.
E3 Incompletely resected NSCLC (R1 or R2).
Does not apply, judged by both models, using F2
Patient has stage IV disease and no resection, 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 F14
No active hepatitis B, C, or HIV infection is reported.
Not eligible A Global Phase III Study of Rilvegostomig or Pembrolizumab Monotherapy for First-Line Treatment of PD-L1-high Metastatic Non-small Cell Lung Cancer I3 Not metE9 Applies, excludesE1 Models disagreeE3 Models disagreeE7 Models disagreeE10 Models disagreeE11 Models disagreeI4 UnknownI6 UnknownI7 UnknownE2 UnknownE4 UnknownE8 UnknownAGE-MIN MetI1 MetI2 MetI5 MetI8 MetI9 MetE5 Does not applyE6 Does not apply Phase 3, AstraZeneca. Nearest site: Lausanne, Switzerland, 137 km away. 11 questions to clarify.
Ask before referring
- 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 targeted 1L (first line) therapies.Facts do not specify status of other actionable drivers like ALK/ROS1.
- I6 Minimum life expectancy of 12 weeks.No specific life expectancy estimate provided in facts.
- I7 Provision of acceptable tumor sample for the central testing prior to randomization.No information on availability of tumor sample for central testing.
- E1 As judged by the investigator, any severe or uncontrolled systemic diseases, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.Writer said does not apply, checker said unknown. No severe uncontrolled systemic diseases mentioned; ECOG 1 and stable cardiac status.
- E2 History of organ transplant.Answer cited no patient fact.
- E3 Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.Writer said does not apply, checker said unknown. No autoimmune disorders or chronic steroid use mentioned.
- E4 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.Answer cited no patient fact.
- E7 Active primary immunodeficiency/active infectious disease(s)Writer said does not apply, checker said unknown. No active infectious diseases or immunodeficiency mentioned.
- E8 Active tuberculosis infectionAnswer cited no patient fact.
- E10 Any prior exposure to an anti-TIGIT (T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain) therapy or any other anticancer therapy targeting immune-regulatory receptors or mechanisms.Writer said does not apply, checker said unknown. No prior exposure to anti-TIGIT or other immune-regulatory therapies.
- E11 Any prior treatment with an anti-PD-1 (programmed cell death protein 1) or anti-PD-L1 (anti-programmed death-ligand 1) agent.Writer said does not apply, checker said unknown. No prior treatment with anti-PD-1 or anti-PD-L1 agents.
What rules the patient out
- I3 Absence of sensitizing EGFR (epidermal growth factor) mutations and ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene 1) rearrangements. Negative assay result is required for all non-squamous histology subtypes.Patient has a sensitizing EGFR exon 19 deletion.
- E9 Any prior systemic therapy received for advanced or mNSCLC (metastatic non-small cell lung cancer).Patient received prior systemic therapy (osimertinib) for advanced NSCLC.
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 NSCLC (non small lung cancer), including all histological subtypes.
Met, judged by both models, using F2
Patient has documented non-small cell lung cancer, adenocarcinoma.
I2 Stage IV mNSCLC (metastatic non-small cell lung cancer) (based on the American Joint Committee on Cancer Edition 8) not amenable to curative treatment.
Met, judged by both models, using F2
Diagnosis is Stage IV metastatic NSCLC, not amenable to cure.
I3 Absence of sensitizing EGFR (epidermal growth factor) mutations and ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene 1) rearrangements. Negative assay result is required for all non-squamous histology subtypes.
Not met, judged by both models, using F3
Patient has a sensitizing EGFR exon 19 deletion.
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 targeted 1L (first line) therapies.
Unknown, judged by first model only
Facts do not specify status of other actionable drivers like ALK/ROS1.
I5 WHO (World Health Organization)/ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1, with no deterioration over the previous 2 weeks prior to baseline at screening and prior to randomization.
Met, judged by both models, using F10
ECOG performance status is 1, which is within the 0-1 range.
I6 Minimum life expectancy of 12 weeks.
Unknown, judged by first model only
No specific life expectancy estimate provided in facts.
I7 Provision of acceptable tumor sample for the central testing prior to randomization.
Unknown, judged by first model only
No information on availability of tumor sample for central testing.
I8 At least one lesion not previously irradiated that qualifies as a RECIST 1.1 (Response Evaluation Criteria in Solid Tumors, Version 1.1) TL (target lesion) 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 (computed tomography) or MRI (magnetic resonance imaging) and is suitable for accurate repeated measurements.
Met, judged by both models, using F11 F8
Right lower lobe mass is 32mm, not irradiated, and measurable.
I9 Adequate organ and bone marrow function
Met, judged by both models, using F12
Lab values for blood counts and organ function are adequate.
E1 As judged by the investigator, any severe or uncontrolled systemic diseases, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
Models disagree, judged by models disagree, using F10 F15
Writer said does not apply, checker said unknown. No severe uncontrolled systemic diseases mentioned; ECOG 1 and stable cardiac status.
E2 History of organ transplant.
Unknown, judged by first model only
Answer cited no patient fact.
E3 Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
Models disagree, judged by models disagree, using F8
Writer said does not apply, checker said unknown. No autoimmune disorders or chronic steroid use mentioned.
E4 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
Answer cited no patient fact.
E5 Presence of small cell and neuroendocrine histology components.
Does not apply, judged by both models, using F2
Histology is adenocarcinoma, not small cell or neuroendocrine.
E6 Brain metastases unless asymptomatic, stable, and not requiring steroids or anticonvulsants for at least 4 weeks prior to start of study intervention.
Does not apply, judged by both models, using F8
Brain metastases are asymptomatic, stable, and not requiring steroids.
E7 Active primary immunodeficiency/active infectious disease(s)
Models disagree, judged by models disagree, using F14
Writer said does not apply, checker said unknown. No active infectious diseases or immunodeficiency mentioned.
E8 Active tuberculosis infection
Unknown, judged by first model only
Answer cited no patient fact.
E9 Any prior systemic therapy received for advanced or mNSCLC (metastatic non-small cell lung cancer).
Applies, excludes, judged by both models, using F4
Patient received prior systemic therapy (osimertinib) for advanced NSCLC.
E10 Any prior exposure to an anti-TIGIT (T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain) therapy or any other anticancer therapy targeting immune-regulatory receptors or mechanisms.
Models disagree, judged by models disagree, using F4 F7
Writer said does not apply, checker said unknown. No prior exposure to anti-TIGIT or other immune-regulatory therapies.
E11 Any prior treatment with an anti-PD-1 (programmed cell death protein 1) or anti-PD-L1 (anti-programmed death-ligand 1) agent.
Models disagree, judged by models disagree, using F7
Writer said does not apply, checker said unknown. No prior treatment with anti-PD-1 or anti-PD-L1 agents.
Not eligible A Study to Assess Zipalertinib Versus Placebo in Participants With Early Stage NSCLC With Uncommon EGFR Mutations, Following Complete Tumor Resection I2 Not metI3 Not metI7 Not metE2 Applies, excludesI4 Models disagreeI5 Models disagreeE3 Models disagreeE4 Models disagreeE7 Models disagreeE8 Models disagreeI8 UnknownE1 UnknownE5 UnknownE6 UnknownE9 UnknownAGE-MIN MetI1 MetI6 Met Phase 3, Taiho Oncology, Inc.. Nearest site: Mulhouse, France, 29 km away. 11 questions to clarify.
Ask before referring
- I4 Complete surgical resection of the primary NSCLC is mandatory with negative surgical margins and systematic lymph node sampling or dissection.Writer said not met, checker said unknown. Patient has stage IV disease and received systemic therapy, implying no complete surgical resection.
- 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.Writer said not met, checker said unknown. Patient has not undergone complete surgical resection, so recovery from surgery is not applicable/met.
- I8 Archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers.Facts do not specify if archival tumor tissue is currently available for submission.
- 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 and no history of wedge resection is mentioned; likely not applicable.
- E4 Past medical history of interstitial lung disease (ILD)/pneumonitis, drug-induced ILD/pneumonitis or any evidence of clinically active ILD/pneumonitis.Writer said does not apply, checker said unknown. Patient has 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).No facts provided regarding ability to swallow tablets or GI absorption issues.
- 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.
- E7 Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) that is unstable or not controlled with treatment.Writer said does not apply, checker said unknown. Patient has no active hepatitis B, C, or HIV infection.
- E8 Active bleeding disorders.Writer said does not apply, checker said unknown. Platelet count is normal (210 x 10^9/L), suggesting no active bleeding disorder.
- E9 Known hypersensitivity to the ingredients in zipalertinib/placebo or any drugs similar in structure or class.No facts provided regarding hypersensitivity to zipalertinib ingredients.
What rules the patient out
- 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 domainPatient has EGFR exon 19 deletion, which is not an exon 20 insertion or uncommon mutation.
- 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 metastasisPatient has known brain metastases, even if stable, which violates the 'no evidence' requirement.
- 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 required stages IB-III A (or IIIB N2).
- 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.Patient received osimertinib, an EGFR inhibitor, which is an excluded prior therapy.
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
Not met, judged by both models, using F3
Patient has EGFR exon 19 deletion, which is not an exon 20 insertion or uncommon mutation.
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
Not met, judged by both models, using F8
Patient has known brain metastases, even if stable, which violates the 'no evidence' requirement.
I4 Complete surgical resection of the primary NSCLC is mandatory with negative surgical margins and systematic lymph node sampling or dissection.
Models disagree, judged by models disagree, using F2 F4
Writer said not met, checker said unknown. Patient has stage IV disease and received systemic therapy, implying no complete surgical resection.
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.
Models disagree, judged by models disagree, using F2 F4
Writer said not met, checker said unknown. Patient has not undergone complete surgical resection, so recovery from surgery is not applicable/met.
I6 Eastern cooperative oncology group performance status (ECOG PS) of 0 or 1.
Met, judged by both models, using F10
Patient's ECOG performance status is 1, which is within the required range of 0 or 1.
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 required stages IB-III A (or IIIB N2).
I8 Archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers.
Unknown, judged by first model only
Facts do not specify if archival tumor tissue is currently available for submission.
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.
Applies, excludes, judged by both models, using F4
Patient received osimertinib, an EGFR inhibitor, which is an excluded prior therapy.
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 and no history of wedge resection is mentioned; likely not applicable.
E4 Past medical history of interstitial lung disease (ILD)/pneumonitis, drug-induced ILD/pneumonitis or any evidence of clinically active ILD/pneumonitis.
Models disagree, judged by models disagree, using F13
Writer said does not apply, checker said unknown. Patient has 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
No facts provided regarding ability to swallow tablets or GI absorption issues.
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.
Models disagree, judged by models disagree, using F14
Writer said does not apply, checker said unknown. Patient has no active hepatitis B, C, or HIV infection.
E8 Active bleeding disorders.
Models disagree, judged by models disagree, using F12
Writer said does not apply, checker said unknown. Platelet count is normal (210 x 10^9/L), suggesting no active bleeding disorder.
E9 Known hypersensitivity to the ingredients in zipalertinib/placebo or any drugs similar in structure or class.
Unknown, judged by first model only
No facts provided regarding hypersensitivity to zipalertinib ingredients.
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 metI9 Not metI12 Not metI5 Models disagreeI16 Models disagreeI1 UnknownI3 UnknownI6 UnknownI8 UnknownI10 UnknownI11 UnknownI13 UnknownI17 UnknownI18 UnknownI19 UnknownI20 UnknownI21 UnknownI22 UnknownI24 UnknownI25 UnknownI26 UnknownI27 UnknownI28 UnknownI29 At screeningI30 At screeningAGE-MIN MetI7 MetI14 MetI15 MetI23 Met Phase 3, ETOP IBCSG Partners Foundation. Nearest site: Bern, Switzerland, 69 km away. 20 questions to clarify.
Ask before referring
- I1 Most important inclusion criteria:The specific text for this criterion is missing from the prompt.
- I3 Requirements for brain metastases:The specific text for this criterion is missing from the prompt.
- 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 unknown. No prior surgery for brain metastases is recorded; only SRS was performed.
- 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 mLNumber of metastases is known (2), but size/volume details are not provided.
- I8 Requirements for patients with melanoma:Criterion applies to melanoma; patient has NSCLC, so applicability is unclear without full text.
- I10 BRAF-mutation status, locally assessed, should be known (previous adjuvant BRAF-targeted therapy is allowed).Criterion applies to melanoma; patient has NSCLC, so applicability is unclear without full text.
- I11 Requirements for patients with NSCLC:The specific text for this criterion is missing from the prompt.
- I13 Known PD-L1 expression status (from primary tumour or from a metastatic lesion, including brain)PD-L1 expression status is not mentioned in the patient facts.
- I16 Karnofsky performance status of 60 or moreWriter said met, checker said unknown. ECOG 1 corresponds to a Karnofsky Performance Status of approximately 90, 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 definitions are not provided in the prompt to determine eligibility.
- 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 mentioned in the patient facts.
- I21 Confirmed or probable leptomeningeal metastases according to EANO ESMO criteriaInvalid answer 'does_not_apply'.
- 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'.
- I24 Patients experiencing seizures controlled by anti-epileptic drugs are eligible.No information is provided regarding seizure history or anti-epileptic drug use.
- I25 Prior whole brain irradiation or focal radiation therapy to the brainInvalid answer 'applies'.
- I26 Prior systemic treatment for brain metastasesInvalid answer 'does_not_apply'.
- I27 Contra-indication for SRSNo information is provided regarding contraindications for SRS.
- 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.Brain metastases were treated with SRS 8 months ago, so they are not newly diagnosed.
- I4 Brain metastases must be previously untreated, except for surgery.Brain metastases were treated with SRS, which is not surgery, so they are not previously untreated.
- I9 Prior treatment, including treatment with immune-checkpoint inhibitors is permitted, but brain metastases must be newly diagnosed and previously untreated (except for surgery).Brain metastases are not newly diagnosed as they were treated 8 months ago.
- I12 Newly diagnosed, treatment-naïve (except for prior surgery) metastatic NSCLC, with or without a targetable oncogenic driver alteration.Patient received prior systemic treatment (osimertinib), so she is not treatment-naïve.
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 prompt.
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 F8
Brain metastases were treated with SRS 8 months ago, so they are not newly diagnosed.
I3 Requirements for brain metastases:
Unknown, judged by first model only
The specific text for this criterion is missing from the prompt.
I4 Brain metastases must be previously untreated, except for surgery.
Not met, judged by both models, using F8
Brain metastases were treated with SRS, which is not surgery, so they are not 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 F8
Writer said not met, checker said unknown. No prior surgery for brain metastases is recorded; only SRS was performed.
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
Unknown, judged by first model only, using F8
Number of metastases is known (2), but size/volume details are not provided.
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 (adenocarcinoma).
I8 Requirements for patients with melanoma:
Unknown, judged by first model only
Criterion applies to melanoma; patient has NSCLC, so applicability is unclear without full text.
I9 Prior treatment, including treatment with immune-checkpoint inhibitors is permitted, but brain metastases must be newly diagnosed and previously untreated (except for surgery).
Not met, judged by both models, using F8
Brain metastases are not newly diagnosed as they were treated 8 months ago.
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, so applicability is unclear without full text.
I11 Requirements for patients with NSCLC:
Unknown, judged by first model only
The specific text for this criterion is missing from the prompt.
I12 Newly diagnosed, treatment-naïve (except for prior surgery) metastatic NSCLC, with or without a targetable oncogenic driver alteration.
Not met, judged by both models, using F4
Patient received prior systemic treatment (osimertinib), so she is not treatment-naïve.
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 mentioned in the patient facts.
I14 Known driver mutation status (from primary tumour or from a metastatic lesion, including brain).
Met, judged by both models, using F3
EGFR exon 19 deletion status is known from tissue NGS.
I15 Age of 18 years or older
Met, judged by both models, using F1
Patient is 61 years old, which is 18 years or older.
I16 Karnofsky performance status of 60 or more
Models disagree, judged by models disagree, using F10
Writer said met, checker said unknown. ECOG 1 corresponds to a Karnofsky Performance Status of approximately 90, 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 definitions are not provided in the prompt to determine eligibility.
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 mentioned in the patient facts.
I21 Confirmed or probable leptomeningeal metastases according to EANO ESMO criteria
Unknown, judged by first model only
Invalid answer 'does_not_apply'.
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.
Met, judged by both models, using F8
Patient is not on steroids, which satisfies the requirement of being off or on stable low dose.
I24 Patients experiencing seizures controlled by anti-epileptic drugs are eligible.
Unknown, judged by first model only
No information is provided regarding seizure history or anti-epileptic drug use.
I25 Prior whole brain irradiation or focal radiation therapy to the brain
Unknown, judged by first model only
Invalid answer 'applies'.
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
No information is provided regarding contraindications for SRS.
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).