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)
- Conditions
- KRAS p.G12C Mutant Advanced Solid Tumors
- Interventions
- Registration Number
- NCT03600883
- Lead Sponsor
- Amgen
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 713
- Men or women greater than or equal to 18 years old.
- Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12C mutation identified through molecular testing.
Exclusion Criteria
- Active brain metastases from non-brain tumors.
- Myocardial infarction within 6 months of study day 1.
- Gastrointestinal (GI) tract disease causing the inability to take oral medication.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1 Dose Exploration Part 1 monotherapy sotorasib Cohorts with food effect and alternative dosing regimens Enrollment into the dose exploration cohorts may be from any eligible solid tumor type. Dose escalation will begin with 2-4 subjects treated at the lowest planned dose level of 180 mg. If no DLT is observed, dose escalation will continue to the next planned dose cohort Phase 1 Dose Expansion Part 2 monotherapy sotorasib Upon completing the dose exploration part of the study, dose expansion may proceed with 3 groups consisting of subjects with KRAS p.G12C mutant advanced solid tumors. Dose expansion in these 3 groups may be done concurrently Phase 1 combination arm with sotorasib and anti PD-1/L1 sotorasib Additional subjects will be enrolled into the combination arm with sotorasib in combination with an anti (PD-1/L1) Phase 1 combination arm with sotorasib and anti PD-1/L1 Anti PD-1/L1 Additional subjects will be enrolled into the combination arm with sotorasib in combination with an anti (PD-1/L1) Phase 1 monotherapy treatment naive advanced NSCLC sotorasib Separate cohort of part 1 dose expansion subjects to evaluate the safety and clinical activity of sotorasib administered orally once daily in subjects with previously untreated advanced non-small cell lung cancer (NSCLC). Drug-drug interaction will be evaluated in 6 of the subjects enrolled in the treatment naive cohort by adding Midazolam alone on Day -1 and in combination with sotorasib on Day 15 of Cycle 1, where each cycle is 21 days. Phase 1 monotherapy treatment naive advanced NSCLC Midazolam Separate cohort of part 1 dose expansion subjects to evaluate the safety and clinical activity of sotorasib administered orally once daily in subjects with previously untreated advanced non-small cell lung cancer (NSCLC). Drug-drug interaction will be evaluated in 6 of the subjects enrolled in the treatment naive cohort by adding Midazolam alone on Day -1 and in combination with sotorasib on Day 15 of Cycle 1, where each cycle is 21 days. Phase 2 monotherapy dose comparison sotorasib Subjects with NSCLC will be enrolled in a dose comparison study evaluating safety and efficacy Phase 1 Does escalation and Expansion monotherapy BID sotorasib BID 2L+solid tumors (fed state)
- Primary Outcome Measures
Name Time Method Primary: Number of subjects with serious adverse events 24 Months Serious adverse events will be a primary outcome measure in the following group:
- Phase 2 monotherapy dose comparisonPrimary: Number of subjects with adverse events of interest 24 Months Adverse events of interest will be a primary outcome measure in the following group:
- Phase 2 monotherapy dose comparisonPrimary: Number of subjects with treatment-emergent adverse events 24 Months Treatment-emergent adverse events will be a primary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapy
* Phase 1 combination arm with sotorasib and anti PD-1/L1
* Phase 1 monotherapy treatment naïve advanced NSCLC
* Phase 2 monotherapy dose comparisonPrimary: Number of subjects with clinically significant changes in physical examination results Baseline to 24 Months Physical examinations will be a primary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapy
* Phase 1 combination arm with sotorasib and anti PD-1/L1Primary: Number of subjects with clinically significant changes on electrocardiograms (ECGs) Baseline to 24 Months ECGs will be a primary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapy
* Phase 1 combination arm with sotorasib and anti PD-1/L1
* Phase 1 monotherapy treatment naïve advanced NSCLCPrimary: Number of subjects with treatment-related adverse events 24 Months Treatment-related adverse events will be a primary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapy
* Phase 1 combination arm with sotorasib and anti PD-1/L1
* Phase 1 monotherapy treatment naïve advanced NSCLCPrimary: Number of subjects with grade ≥3 treatment-emergent adverse events 24 Months Grade ≥3 treatment-emergent adverse events will be a primary outcome measure in the following group:
- Phase 2 monotherapy dose comparisonPrimary: Number of subjects with clinically significant changes in vital signs Baseline to 24 Months Vital signs will be a primary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapy
* Phase 1 combination arm with sotorasib and anti PD-1/L1
* Phase 1 monotherapy treatment naïve advanced NSCLCPrimary: Duration of response (DOR) as assessed by RECIST 1.1 criteria 24 Months DOR will be a primary outcome measure in the following group:
- Phase 1 monotherapy treatment naïve advanced NSCLCPrimary: Number of subjects with dose-limiting toxicities (DLTs) 21 Days DLTs will be a primary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapy
* Phase 1 combination arm with sotorasib and anti PD-1/L1
* Phase 1 monotherapy treatment naïve advanced NSCLCPrimary: Number of subjects with clinically significant changes in clinical laboratory values Baseline to 24 Months Abnormal clinical laboratory values will be a primary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapy
* Phase 1 combination arm with sotorasib and anti PD-1/L1
* Phase 1 monotherapy treatment naïve advanced NSCLCPrimary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria 24 Months ORR will be a primary outcome measure in the following group:
* Phase 1 monotherapy treatment naïve advanced NSCLC
* Phase 2 monotherapy
* Phase 2 monotherapy dose comparisonPrimary: Disease control as assessed by RECIST 1.1 criteria 24 Months Disease control will be a primary outcome measure in the following group:
- Phase 1 monotherapy treatment naïve advanced NSCLCPrimary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria 24 Months Duration of SD will be a primary outcome measure in the following group:
- Phase 1 monotherapy treatment naïve advanced NSCLCPrimary: Time to response (TTR) as assessed by RECIST 1.1 criteria 24 Months TTR will be a primary outcome measure in the following group:
- Phase 1 monotherapy treatment naïve advanced NSCLC
- Secondary Outcome Measures
Name Time Method Secondary: Terminal half-life (t1/2) of midazolam 16 Days t1/2 of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group:
- Phase 1 monotherapy treatment naïve advanced NSCLCSecondary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria 24 Months ORR will be a secondary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapy
* Phase 1 combination arm with sotorasib and anti PD-1/L1Secondary: Duration of response (DOR) as assessed by RECIST 1.1 criteria 24 Months DOR will be a secondary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapy
* Phase 2 monotherapy
* Phase 1 combination arm with sotorasib and anti PD-1/L1
* Phase 2 monotherapy dose comparisonSecondary: Disease control as assessed by RECIST 1.1 criteria 24 Months DOR will be a secondary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapy
* Phase 2 monotherapy
* Phase 1 combination arm with sotorasib and anti PD-1/L1
* Phase 2 monotherapy dose comparisonSecondary: Progression-free survival (PFS) as assessed by RECIST 1.1 criteria 24 Months PFS will be a secondary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapy
* Phase 2 monotherapy
* Phase 1 combination arm with sotorasib and anti PD-1/L1
* Phase 2 monotherapy dose comparison
* Phase 1 monotherapy treatment naïve advanced NSCLCSecondary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria 24 Months Duration of SD will be a secondary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapy
* Phase 1 combination arm with sotorasib and anti PD-1/L1Secondary: Depth of response (best percentage change from baseline in lesion sum diameters) as assessed by RECIST 1.1 criteria Baseline to 24 Months Depth of response will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparisonSecondary: Time to response (TTR) as assessed by RECIST 1.1 criteria 24 Months DOR will be a secondary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapy
* Phase 2 monotherapy
* Phase 1 combination arm with sotorasib and anti PD-1/L1
* Phase 2 monotherapy dose comparisonSecondary: Overall survival (OS) 24 Months OS will be a secondary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapy
* Phase 2 monotherapy
* Phase 1 combination arm with sotorasib and anti PD-1/L1
* Phase 2 monotherapy dose comparison
* Phase 1 monotherapy treatment naïve advanced NSCLCSecondary: sotorasib exposure and QTc interval relationship 24 Months sotorasib exposure and QTc interval relationship will be a secondary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapySecondary: Progression-free survival (PFS) at 6 months 6 Months PFS at 6 months will be a secondary outcome measure for the following group:
- Phase 2 monotherapySecondary: Progression-free survival (PFS) at 12 months 12 Months PFS at 12 months will be a secondary outcome measure for the following group:
- Phase 2 monotherapySecondary: Overall survival (OS) at 12 months 12 Months OS at 12 months will be a secondary outcome measure for the following group:
- Phase 2 monotherapySecondary: Number of subjects with treatment-emergent adverse events 24 Months Treatment-emergent adverse events will be a secondary outcome measure for the following group:
- Phase 2 monotherapySecondary: Number of subjects with grade ≥3 treatment-emergent adverse events 24 Months Grade ≥3 treatment-emergent adverse events will be a secondary outcome measure for the following group:
- Phase 2 monotherapySecondary: Impact of treatment on disease-related symptoms and health related quality of life (HRQOL) as assessed by EORTC QLQ-C30 24 Months Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparisonSecondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by disease-specific modules Quality-of-Life Questionnaire Lung Cancer Module (QLQ LC13) 24 Months Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparisonSecondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by non-small cell lung cancer symptom assessment questionnaire (NSCLC SAQ) for NSCLC 24 Months Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparisonSecondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Severity (PGIS) 24 Months Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparisonSecondary: 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 24 Months Impact of treatment on disease-related symptoms and HRQOL will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparisonSecondary: Treatment-related symptoms and impact on the subject as assessed by EORTC QLQ-C30 24 Months Treament related symptoms and impact on the subject will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparisonSecondary: 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) 24 Months Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparisonSecondary: 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) 24 Months Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparisonSecondary: Change from baseline in physical function as assessed by EORTC QLQ-C30 Baseline to 24 Months Treatment-related symptoms and impact on the subject will be a secondary outcome measure for the following group:
- Phase 2 monotherapy dose comparisonSecondary: Plasma concentration (Cmax) of sotorasib 15 Weeks Cmax will be a secondary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapy
* Phase 2 monotherapy
* Phase 1 combination arm with sotorasib and anti PD-1/L1
* Phase 1 monotherapy treatment naïve advanced NSCLC
* Phase 2 monotherapy dose comparisonSecondary: Plasma concentration (Cmax) of midazolam 16 Days Cmax of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group:
- Phase 1 monotherapy treatment naïve advanced NSCLCSecondary: Time to achieve Cmax (Tmax) of sotorasib 15 Weeks Tmax will be a secondary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapy
* Phase 2 monotherapy
* Phase 1 combination arm with sotorasib and anti PD-1/L1
* Phase 1 monotherapy treatment naïve advanced NSCLCSecondary: Area under the plasma concentration-time curve (AUC) of sotorasib 15 Weeks AUC will be a secondary outcome measure for the following groups:
* Phase 1 Dose Exploration Part 1 monotherapy
* Phase 1 Dose Expansion Part 2 monotherapy
* Phase 2 monotherapy
* Phase 1 combination arm with sotorasib and anti PD-1/L1
* Phase 1 monotherapy treatment naïve advanced NSCLC
* Phase 2 monotherapy dose comparisonSecondary: Area under the plasma concentration-time curve (AUC) of midazolam 16 Days AUC of midazolam will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group:
- Phase 1 monotherapy treatment naïve advanced NSCLCSecondary: Clearance of midazolam from the plasma 16 Days Clearance of midazolam from the plasma will be a secondary outcome measure for the subgroup of subjects who were administered midazolam in the following group:
- Phase 1 monotherapy treatment naïve advanced NSCLC
Trial Locations
- Locations (133)
City of Hope National Medical Center
🇺🇸Duarte, California, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
University of California at SF
🇺🇸San Francisco, California, United States
Sarcoma Oncology Research Center LLC
🇺🇸Santa Monica, California, United States
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
Sarah Cannon Research Institute at HealthONE
🇺🇸Denver, Colorado, United States
Smilow Cancer Hospital at Yale New Haven
🇺🇸New Haven, Connecticut, United States
Medical Oncology Hematology Consultants Helen F Graham Cancer Center
🇺🇸Newark, Delaware, United States
University of Florida Health
🇺🇸Gainesville, Florida, United States
AdventHealth Orlando Infusion Center
🇺🇸Orlando, Florida, United States
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