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RecruitingInterventionalPhase 3

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)

NCT ID: NCT05920356Sponsor: AmgenLast updated: 2026-06-04

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.

Arms & interventions

  • DrugSotorasib

    Oral administration

  • DrugPembrolizumab

    Intravenous administration

Outcome measures

Primary

  • 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).

    Time frame: Approximately 2.5 years

  • Overall Survival (OS)

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

    Time frame: Approximately 2.5 years

Secondary

  • Objective Response Rate (ORR)

    Time frame: 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

    Time frame: From Baseline to Week 12

  • Change in Quality-of-Life Questionnaire Lung Cancer 13 (QLQ-LC13) Symptoms of Dyspnea Subscale

    Time frame: From Baseline to Week 12

  • Change in QLQ-LC13 Symptoms of Cough Subscale

    Time frame: From Baseline to Week 12

  • Change in QLQ-LC13 Symptoms of Chest Pain Subscale

    Time frame: From Baseline to Week 12

  • Change in Physical Function as Measured by QLQ-C30

    Time frame: From Baseline to Week 12

  • Change in Global Health Status as Measured by QLQ-C30

    Time frame: From Baseline to Week 12

  • Progression-free Survival 2 (PFS2)

    Time frame: From Baseline up to EOS (approximately 5.5 years)

  • Change in QLQ-LC13 Subscale Scores

    Time frame: From Baseline up to EOS (approximately 5.5 years)

  • Change in QLQ-C30 Subscale Scores

    Time frame: From Baseline up to EOS (approximately 5.5 years)

  • Time to Deterioration in QLC-LC13 Subscale Scores

    Time frame: From Baseline to Week 12

  • Time to Deterioration in QLC-C30 Subscale Scores

    Time frame: From Baseline to Week 12

  • Change in Summary Scores and Visual Analogue Scale (VAS) Scores

    Time frame: From Baseline up to EOS (approximately 5.5 years)

  • Duration of Response

    Time frame: From Baseline up to EOS (approximately 5.5 years)

  • Time to Response

    Time frame: From Baseline up to EOS (approximately 5.5 years)

  • Disease Control

    Time frame: From Baseline up to EOS (approximately 5.5 years)

  • PFS

    Time frame: From Baseline up to EOS (approximately 5.5 years)

  • Objective Response

    Time frame: From Baseline up to EOS (approximately 5.5 years)

  • Number of Participants With Treatment-Emergent Adverse Events

    Time frame: From Baseline up to EOS (approximately 5.5 years)

  • Number of Participants With Clinically Significant Changes in Vital Signs

    Time frame: From Baseline up to EOS (approximately 5.5 years)

  • Number of Participants With Clinically Significant Changes in Clinical Laboratory Tests

    Time frame: From Baseline up to EOS (approximately 5.5 years)

  • Maximum Plasma Concentration (Cmax) of Sotorasib

    Time frame: Pre-dose Day 1 up to Day 64

  • Minimum Plasma Concentration (Cmin) of Sotorasib

    Time frame: Pre-dose Day 1 up to Day 64

  • Area Under The Curve (AUC) of Sotorasib

    Time frame: Pre-dose Day 1 up to Day 64

Eligibility criteria

Sex: AllAge: 18 Years to 100 YearsHealthy volunteers: No
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

Study locations (21)

Sansum Clinic

Santa Barbara, California, 93105

Recruiting

Medical Oncology Hematology Consultants Helen F Graham Cancer Center

Newark, Delaware, 19713

Recruiting

University of Illinois Chicago

Chicago, Illinois, 60612

Recruiting

Illinois Cancer Specialists

Niles, Illinois, 60714

Recruiting

Norton Cancer Institute - Brownsboro

Louisville, Kentucky, 40241

Completed

Reliant Medical Group Inc

Worcester, Massachusetts, 01606

Recruiting

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87131

Recruiting

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Terminated

Messino Cancer Centers Asheville

Asheville, North Carolina, 28806

Recruiting

Duke University Medical Center

Durham, North Carolina, 27710

Recruiting

FirstHealth Cancer Center

Pinehurst, North Carolina, 28374

Recruiting

Alliance Cancer Specialists - Media

Media, Pennsylvania, 19063

Recruiting

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232

Terminated

Regional One Health

Memphis, Tennessee, 38103

Recruiting

Sarah Cannon Research Institute

Nashville, Tennessee, 37203

Recruiting

United States Oncology Regulatory Affairs Corporate Office

Nashville, Tennessee, 37203

Recruiting

Oncology Consultants PA

Houston, Texas, 77030

Recruiting

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting

US Oncology Research Investigational Products Center

Irving, Texas, 75063

Recruiting

Vista Oncology Inc PS

Olympia, Washington, 98506

Recruiting

Mercyhealth

Janesville, Wisconsin, 53548

Recruiting
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) | Cancerify