A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)

Study Overview
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Brief Summary
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The primary objective of this study is to compare progression-free survival (PFS) in participants who receive sotorasib with platinum doublet chemotherapy versus participants who receive pembrolizumab with platinum doublet chemotherapy.

Official Title
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A Phase 3, Multicenter, Randomized, Open-label Study Evaluating Efficacy of Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Subjects With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers, Negative for PD-L1, and Positive for KRAS p.G12C (CodeBreaK 202)

Conditions
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Non-Small Cell Lung Cancer (NSCLC)

Intervention / Treatment
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* Drug: Sotorasib
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of nonsquamous stage IV or advanced Stage IIIB or IIIC NSCLC with KRAS p. G12C mutation and negative for PD-L1 expression by central testing or local laboratory testing confirmed through central testing No history of systemic anticancer therapy in metastatic/non-curable settings Eastern Cooperative Oncology Group (ECOG) ≤ 1 Exclusion Criteria: Mixed histology NSCLC with either small-cell or large-cell neuroendocrine cell component or predominant squamous cell histology Participants with tumors known to harbor molecular alterations for which targeted therapy is locally approved Symptomatic (treated or untreated) brain metastases Gastrointestinal (GI) tract disease causing the inability to take oral medication Myocardial infarction within 6 months of randomization, unstable arrhythmias, or unstable angina Prior therapy with a KRAS G12C inhibitor

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sotorasib combined with carboplatin and pemetrexed<br>Sotorasib administered in combination with carboplatin and pemetrexed. | Drug: Sotorasib<br>* Oral administration<br>* Other names: LUMAKRAS ®;|
| Active Comparator: Pembrolizumab combined with carboplatin and pemetrexed<br>Pembrolizumab administered in combination with carboplatin and pemetrexed. | Drug: Pembrolizumab<br>* Intravenous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS is defined as the time from randomization until the first documentation of radiologic disease progression or death due to any cause, whichever occurs first. Progression will be based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, per Blinded Independent Central Review (BICR). | From Baseline up to end of study (EOS) (approximately 5.5 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective response is defined as the best overall response of complete response (CR) or partial response (PR), based on RECIST v1.1, per BICR. | From Baseline up to EOS (approximately 5.5 years) | 
| Overall Survival (OS) | OS is defined as the time from randomization until death due to any cause. | From Baseline up to EOS (approximately 5.5 years) | 
| Change in Quality-of-Life Questionnaire Core 30 (QLQ-C30) Dyspnea Domain Score |  | From Baseline to Week 12 | 
| Change in Quality-of-Life Questionnaire Lung Cancer 13 (QLQ-LC13) Symptoms of Dyspnea Subscale |  | From Baseline to Week 12 | 
| Change in QLQ-LC13 Symptoms of Cough Subscale |  | From Baseline to Week 12 | 
| Change in QLQ-LC13 Symptoms of Chest Pain Subscale |  | From Baseline to Week 12 | 
| Change in Physical Function as Measured by QLQ-C30 |  | From Baseline to Week 12 | 
| Change in Global Health Status as Measured by QLQ-C30 |  | From Baseline to Week 12 | 
| Progression-free Survival 2 (PFS2) | PFS2 is defined as the time from randomization to progression per investigator after initiation of new anticancer therapy or treatment beyond progression (ie, second progression) or death from any cause, whichever occurs first. | From Baseline up to EOS (approximately 5.5 years) | 
| Change in QLQ-LC13 Subscale Scores |  | From Baseline up to EOS (approximately 5.5 years) | 
| Change in QLQ-C30 Subscale Scores |  | From Baseline up to EOS (approximately 5.5 years) | 
| Time to Deterioration in QLC-LC13 Subscale Scores |  | From Baseline to Week 12 | 
| Time to Deterioration in QLC-C30 Subscale Scores |  | From Baseline to Week 12 | 
| Change in Summary Scores and Visual Analogue Scale (VAS) Scores | Measured by EuroQol-5 Dimension (EQ-5D-5L). | From Baseline up to EOS (approximately 5.5 years) | 
| Duration of Response | Duration of response is defined as the time from the first documentation of objective response until the first documentation of disease progression per BICR or death due to any cause, whichever occurs first. | From Baseline up to EOS (approximately 5.5 years) | 
| Time to Response | Defined as the time from randomization to first evidence of PR or CR per BICR. | From Baseline up to EOS (approximately 5.5 years) | 
| Disease Control | Defined as CR plus PR plus stable disease based on RECIST v1.1 per BICR. | From Baseline up to EOS (approximately 5.5 years) | 
| PFS | Based on investigator tumor assessments per RECIST v1.1. | From Baseline up to EOS (approximately 5.5 years) | 
| Objective Response | Based on investigator tumor assessments per RECIST v1.1. | From Baseline up to EOS (approximately 5.5 years) | 
| Number of Participants With Treatment-Emergent Adverse Events |  | From Baseline up to EOS (approximately 5.5 years) | 
| Number of Participants With Clinically Significant Changes in Vital Signs |  | From Baseline up to EOS (approximately 5.5 years) | 
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Tests |  | From Baseline up to EOS (approximately 5.5 years) | 
| Maximum Plasma Concentration (Cmax) of Sotorasib |  | Pre-dose Day 1 up to Day 64 | 
| Minimum Plasma Concentration (Cmin) of Sotorasib |  | Pre-dose Day 1 up to Day 64 | 
| Area Under The Curve (AUC) of Sotorasib |  | Pre-dose Day 1 up to Day 64 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oncology, Lung Cancer, PD-L1, KRAS p.G12C, Sotorasib, Pembrolizumab, Carboplatin, Pemetrexed, CodeBreaK 202, NSCLC, PD-L1 Negative, AMG 510, LUMAKRAS ®, LUMYKRAS ®