Protocol No.: OCR24302
Sponsor Protocol No.: 20170543; 20170543;AMG510
Protocol Title.: A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of AMG 510 in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreaK 100)
Principal Investigator: George, Thomas
Objective: Evaluate the safety and tolerability of AMG 510 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.
Phase: Phase I/II
Age Group: Adult
Age: 18 Years - 100 Years
Experimental: Phase 1 Dose Exploration Part 1 monotherapyCohorts 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
Experimental: Phase 1 Dose Expansion Part 2 monotherapyUpon 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
Experimental: Phase 2 monotherapyAdditional subjects will be enrolled in the dose expansion to confirm the recommended phase 2 dose. Enrollment into phase 2 will be opened after confirmation of the recommended phase 2 dose
Experimental: Phase 1 combination arm with AMG 510 and anti PD-1/L1Additional subjects will be enrolled into the combination arm with AMG 510 in combination with an anti (PD-1/L1)
Experimental: Phase 1 monotherapy treatment naive advanced NSCLCSeparate cohort of part 1 dose expansion subjects to evaluate the safety and clinical activity of AMG 510 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 AMG 510 on Day 15 of Cycle 1, where each cycle is 21 days.
Experimental: Phase 2 monotherapy dose comparisonSubjects with NSCLC will be enrolled in a dose comparison study evaluating safety and efficacy
Detailed Eligibility: Inclusion Criteria: - 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.