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)

Purpose

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.

Condition

  • KRAS p.G12C Mutant Advanced Solid Tumors

Eligibility

Eligible Ages
Between 18 Years and 100 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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
  • Drug: sotorasib
    Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
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
  • Drug: sotorasib
    Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
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)
  • Drug: sotorasib
    Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
  • Drug: Anti PD-1/L1
    Administered as an intravenous (IV) infusion
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.
  • Drug: sotorasib
    Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
  • Drug: Midazolam
    Administered as an oral hydrochloride (HCI) syrup
Experimental
Phase 2 monotherapy dose comparison 		Subjects with NSCLC will be enrolled in a dose comparison study evaluating safety and efficacy
  • Drug: sotorasib
    Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation
Experimental
Phase 1 Does escalation and Expansion monotherapy BID 		BID 2L+solid tumors (fed state)
  • Drug: sotorasib
    Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation

More Details

Status
Active, not recruiting
Sponsor
Amgen

Study Contact

For general questions about clinical trials, contact Research Support Services at (615) 322-7343 or research.support.services@vumc.org