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

Eligibility Criteria

Sex

ALL

Age

18 Years - 100 Years

Healthy Volunteers

Not accepted

Interventions

• sotorasib — DRUG
  Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
• Anti PD-1/L1 — DRUG
  Administered as an intravenous (IV) infusion
• Midazolam — DRUG
  Administered as an oral hydrochloride (HCI) syrup

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.

Key Dates

Start date

Aug 27, 2018

Status verified

Mar 2026

Primary completion

May 30, 2026

Completion

May 30, 2026

Study Design

Enrollment

713 participants (actual)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Phase 1 Dose Exploration Part 1 monotherapy
  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
• Experimental: Phase 1 Dose Expansion Part 2 monotherapy
  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
• Experimental: Phase 1 combination arm with sotorasib and anti PD-1/L1
  Additional subjects will be enrolled into the combination arm with sotorasib in combination with an anti (PD-1/L1)
• Experimental: Phase 1 monotherapy treatment naive advanced NSCLC
  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.
• Experimental: Phase 2 monotherapy dose comparison
  Subjects with NSCLC will be enrolled in a dose comparison study evaluating safety and efficacy
• Experimental: Phase 1 Does escalation and Expansion monotherapy BID
  BID 2L+solid tumors (fed state)

Primary Outcome Measure

Primary: Number of subjects with treatment-emergent adverse events [ Time Frame: 24 Months ]

Locations (39)

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