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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)

Phase 3
Recruiting
Conditions
Non-Small Cell Lung Cancer (NSCLC)
Interventions
Registration Number
NCT05920356
Lead Sponsor
Amgen
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
750
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Sotorasib combined with carboplatin and pemetrexedSotorasibSotorasib administered in combination with carboplatin and pemetrexed.
Pembrolizumab combined with carboplatin and pemetrexedPembrolizumabPembrolizumab administered in combination with carboplatin and pemetrexed.
Primary Outcome Measures
NameTimeMethod
Overall Survival (OS)Approximately 2.5 years

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

Progression-free Survival (PFS)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 Outcome Measures
NameTimeMethod
Objective Response Rate (ORR)From Baseline up to end of study (EOS) (approximately 5.5 years)

Objective response is defined as the best overall response of complete response (CR) or partial response (PR), based on RECIST v1.1, per BICR.

Change in Quality-of-Life Questionnaire Core 30 (QLQ-C30) Dyspnea Domain ScoreFrom Baseline to Week 12
Change in Quality-of-Life Questionnaire Lung Cancer 13 (QLQ-LC13) Symptoms of Dyspnea SubscaleFrom Baseline to Week 12
Change in QLQ-LC13 Symptoms of Cough SubscaleFrom Baseline to Week 12
Change in QLQ-LC13 Symptoms of Chest Pain SubscaleFrom Baseline to Week 12
Change in Physical Function as Measured by QLQ-C30From Baseline to Week 12
Change in Global Health Status as Measured by QLQ-C30From Baseline to Week 12
Progression-free Survival 2 (PFS2)From Baseline up to EOS (approximately 5.5 years)

PFS2 is defined as the time from randomization to progression per investigator after initiation of new anticancer therapy or death from any cause, whichever occurs first.

Change in QLQ-LC13 Subscale ScoresFrom Baseline up to EOS (approximately 5.5 years)
Change in QLQ-C30 Subscale ScoresFrom Baseline up to EOS (approximately 5.5 years)
Time to Deterioration in QLC-LC13 Subscale ScoresFrom Baseline to Week 12
Time to Deterioration in QLC-C30 Subscale ScoresFrom Baseline to Week 12
Change in Summary Scores and Visual Analogue Scale (VAS) ScoresFrom Baseline up to EOS (approximately 5.5 years)

Measured by EuroQol-5 Dimension (EQ-5D-5L).

Duration of ResponseFrom Baseline up to EOS (approximately 5.5 years)

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.

Time to ResponseFrom Baseline up to EOS (approximately 5.5 years)

Defined as the time from randomization to first evidence of PR or CR per BICR.

Disease ControlFrom Baseline up to EOS (approximately 5.5 years)

Defined as CR plus PR plus stable disease based on RECIST v1.1 per BICR.

PFSFrom Baseline up to EOS (approximately 5.5 years)

Based on investigator tumor assessments per RECIST v1.1.

Objective ResponseFrom Baseline up to EOS (approximately 5.5 years)

Based on investigator tumor assessments per RECIST v1.1.

Number of Participants With Treatment-Emergent Adverse EventsFrom Baseline up to EOS (approximately 5.5 years)
Number of Participants With Clinically Significant Changes in Vital SignsFrom Baseline up to EOS (approximately 5.5 years)
Number of Participants With Clinically Significant Changes in Clinical Laboratory TestsFrom Baseline up to EOS (approximately 5.5 years)
Maximum Plasma Concentration (Cmax) of SotorasibPre-dose Day 1 up to Day 64
Minimum Plasma Concentration (Cmin) of SotorasibPre-dose Day 1 up to Day 64
Area Under The Curve (AUC) of SotorasibPre-dose Day 1 up to Day 64

Trial Locations

Locations (370)

Sansum Clinic

🇺🇸

Santa Barbara, California, United States

Medical Oncology Hematology Consultants Helen F Graham Cancer Center

🇺🇸

Newark, Delaware, United States

University of Illinois Chicago

🇺🇸

Chicago, Illinois, United States

Illinois Cancer Specialists

🇺🇸

Niles, Illinois, United States

Norton Cancer Institute - Brownsboro

🇺🇸

Louisville, Kentucky, United States

Reliant Medical Group Inc

🇺🇸

Worcester, Massachusetts, United States

University of New Mexico Cancer Center

🇺🇸

Albuquerque, New Mexico, United States

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

Duke University

🇺🇸

Durham, North Carolina, United States

FirstHealth Cancer Center

🇺🇸

Pinehurst, North Carolina, United States

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Sansum Clinic
🇺🇸Santa Barbara, California, United States

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