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)

Amgen677 sites in 7 countries750 target enrollmentNovember 16, 2023

ConditionsNon-Small Cell Lung Cancer (NSCLC)

InterventionsPembrolizumab Sotorasib

Overview

Phase: Phase 3
Intervention: Pembrolizumab
Conditions: Non-Small Cell Lung Cancer (NSCLC)
Sponsor: Amgen
Enrollment: 750
Locations: 677
Primary Endpoint: Overall Survival (OS)
Status: Recruiting
Last Updated: yesterday

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The primary objectives are to compare progression-free survival (PFS) and overall survival (OS) in participants who receive sotorasib with platinum doublet chemotherapy versus participants who receive pembrolizumab with platinum doublet chemotherapy.

Registry

clinicaltrials.gov

Start Date

November 16, 2023

End Date

June 29, 2032

Last Updated

yesterday

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Amgen

Responsible Party

Sponsor

Eligibility Criteria

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 as a front-line therapy
•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

Arms & Interventions

Pembrolizumab combined with carboplatin and pemetrexed

Pembrolizumab administered in combination with carboplatin and pemetrexed.

Intervention: Pembrolizumab

Sotorasib combined with carboplatin and pemetrexed

Sotorasib administered in combination with carboplatin and pemetrexed.

Intervention: Sotorasib

Outcomes

Primary Outcomes

Overall Survival (OS)

Time Frame: Approximately 2.5 years

OS is defined as the time from randomization until death due to any cause.

Progression-free Survival (PFS)

Time Frame: Approximately 2.5 years

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).

Secondary Outcomes

Objective Response Rate (ORR)(From Baseline up to end of study (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 Physical Function as Measured by QLQ-C30(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 Global Health Status as Measured by QLQ-C30(From Baseline to Week 12)
Progression-free Survival 2 (PFS2)(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(From Baseline up to EOS (approximately 5.5 years))
Duration of Response(From Baseline up to EOS (approximately 5.5 years))
Time to Response(From Baseline up to EOS (approximately 5.5 years))
Disease Control(From Baseline up to EOS (approximately 5.5 years))
PFS(From Baseline up to EOS (approximately 5.5 years))
Objective Response(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)