A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of sotorasib (AMG 510) in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreaK 100)
Study Details
Evaluate the safety and tolerability of sotorasib in adult subjects with KRAS p.G12C mutant advanced solid tumors.
Estimate the maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) in adult subjects with KRAS p.G12C mutant advanced solid tumors.
Protocol Summary
Primary: Number of subjects with treatment-emergent adverse events
Timeframe: 24 Months
Primary: Number of subjects with treatment-related adverse events
Timeframe: 24 Months
Primary: Number of subjects with grade ≥3 treatment-emergent adverse events
Timeframe: 24 Months
Primary: Number of subjects with serious adverse events
Timeframe: 24 Months
Primary: Number of subjects with adverse events of interest
Timeframe: 24 Months
Primary: Number of subjects with clinically significant changes in vital signs
Timeframe: Baseline to 24 Months
Primary: Number of subjects with clinically significant changes in physical examination results
Timeframe: Baseline to 24 Months
Primary: Number of subjects with clinically significant changes on electrocardiograms (ECGs)
Timeframe: Baseline to 24 Months
Primary: Number of subjects with clinically significant changes in clinical laboratory values
Timeframe: Baseline to 24 Months
Primary: Number of subjects with dose-limiting toxicities (DLTs)
Timeframe: 21 Days
Primary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria
Timeframe: 24 Months
Primary: Duration of response (DOR) as assessed by RECIST 1.1 criteria
Timeframe: 24 Months
Primary: Disease control as assessed by RECIST 1.1 criteria
Timeframe: 24 Months
Primary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria
Timeframe: 24 Months
Primary: Time to response (TTR) as assessed by RECIST 1.1 criteria
Timeframe: 24 Months
Secondary: Plasma concentration (Cmax) of sotorasib
Timeframe: 15 Weeks
Secondary: Plasma concentration (Cmax) of midazolam
Timeframe: 16 Days
Secondary: Time to achieve Cmax (Tmax) of sotorasib
Timeframe: 15 Weeks
Secondary: Area under the plasma concentration-time curve (AUC) of sotorasib
Timeframe: 15 Weeks
Secondary: Area under the plasma concentration-time curve (AUC) of midazolam
Timeframe: 16 Days
Secondary: Clearance of midazolam from the plasma
Timeframe: 16 Days
Secondary: Terminal half-life (t1/2) of midazolam
Timeframe: 16 Days
Secondary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria
Timeframe: 24 Months
Secondary: Duration of response (DOR) as assessed by RECIST 1.1 criteria
Timeframe: 24 Months
Secondary: Disease control as assessed by RECIST 1.1 criteria
Timeframe: 24 Months
Secondary: Progression-free survival (PFS) as assessed by RECIST 1.1 criteria
Timeframe: 24 Months
Secondary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria
Timeframe: 24 Months
Secondary: Depth of response (best percentage change from baseline in lesion sum diameters) as assessed by RECIST 1.1 criteria
Timeframe: Baseline to 24 Months
Secondary: Time to response (TTR) as assessed by RECIST 1.1 criteria
Timeframe: 24 Months
Secondary: Overall survival (OS)
Timeframe: 24 Months
Secondary: sotorasib exposure and QTc interval relationship
Timeframe: 24 Months
Secondary: Progression-free survival (PFS) at 6 months
Timeframe: 6 Months
Secondary: Progression-free survival (PFS) at 12 months
Timeframe: 12 Months
Secondary: Overall survival (OS) at 12 months
Timeframe: 12 Months
Secondary: Number of subjects with treatment-emergent adverse events
Timeframe: 24 Months
Secondary: Number of subjects with grade ≥3 treatment-emergent adverse events
Timeframe: 24 Months
Secondary: Impact of treatment on disease-related symptoms and health related quality of life (HRQOL) as assessed by EORTC QLQ-C30
Timeframe: 24 Months
Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by disease-specific modules Quality-of-Life Questionnaire Lung Cancer Module (QLQ LC13)
Timeframe: 24 Months
Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by non-small cell lung cancer symptom assessment questionnaire (NSCLC SAQ) for NSCLC
Timeframe: 24 Months
Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Severity (PGIS)
Timeframe: 24 Months
Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Change (PGIC) in cough, dyspnea and chest pain for NSCLC
Timeframe: 24 Months
Secondary: Treatment-related symptoms and impact on the subject as assessed by EORTC QLQ-C30
Timeframe: 24 Months
Secondary: Treatment-related symptoms and impact on the subject as assessed by selected questions from the Patient-reported Outcome of the Common Terminology Criteria for Adverse Events (PRO-CTCAE library)
Timeframe: 24 Months
Secondary: Treatment-related symptoms and impact on the subject as assessed by a single item about symptom bother, item GP5 of the Functional Assessment of Cancer Therapy - General (FACT-G)
Timeframe: 24 Months
Secondary: Change from baseline in physical function as assessed by EORTC QLQ-C30
Timeframe: Baseline to 24 Months