Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients

Sponsor: Verastem, Inc.

Sponsor score: 0
Inactive

ClinicalTrials ID:NCT05074810

Patient View

This Phase 1/2 study evaluates the safety and efficacy of avutometinib and sotorasib, with or without defactinib, in KRAS G12C NSCLC patients. Eligible participants are adults with measurable disease, ECOG ≤ 1, and adequate organ function. Exclusions include recent systemic therapy, certain infections, and prior MEK inhibitor use. The study involves dose expansion based on Part A results.

Patient Parameters

Program Overview

This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with sotorasib with or without defactinib in patients with KRAS G12C Non-Small Cell Lung Cancer (NSCLC) in patients who have been exposed to prior G12C inhibitor and those who have not been exposed to prior G12C inhibitor.

Description

This is a multicenter, non-randomized, open-label Phase 1/2 study designed to evaluate safety and tolerability and efficacy of avutometinib (VS-6766) in combination with sotorasib with or without defactinib in patients with KRAS G12C mutant NSCLC.

Eligibility Criteria

Inclusion Criteria

  • Male or female patients ≥ 18 years of age
  • Histologic or cytologic evidence of NSCLC
  • Known KRAS G12C mutation
  • Either exposed or not exposed to a KRAS inhibitor to be included in Part A (avutometinib + sotorasib + defactinib) and not exposed to KRAS inhibitor to be included in Part B (avutometinib + sotorasib + defactinib), Cohort 1
  • Received at least 1 dose of a G12C inhibitor to be included in Part B, Cohort 2 (avutometinib + sotorasib + defactinib)
  • Must have received appropriate treatment with at least one prior systemic regimen, but no more than 2 prior regimens, for Stage 3B-C or 4 NSCLC
  • Measurable disease according to RECIST 1.1
  • An Eastern Cooperative Group (ECOG) performance status ≤ 1
  • Adequate organ function
  • Adequate recovery from toxicities related to prior treatments
  • Agreement to use highly effective method of contraceptive

Exclusion Criteria

  • Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy
  • History of prior malignancy, with the exception of curatively treated malignancies
  • Major surgery within 4 weeks, minor surgery within 2 weeks (excluding placement of vascular access)
  • History of treatment with a direct and specific inhibitor of MEK
  • Exposure to strong CYP3A4 inhibitors or inducers within 14 days prior to the first dose and during the course of therapy
  • Symptomatic brain metastases requiring steroids or other local interventions.
  • Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy
  • Known hepatitis B, hepatitis C, or human immunodeficiency virus infection that is active
  • Active skin disorder that has required systemic therapy within the past year
  • History of rhabdomyolysis
  • Concurrent ocular disorders
  • Concurrent heart disease or severe obstructive pulmonary disease
  • Inability to swallow oral medications
  • Female patients that are pregnant or breastfeeding
  • Previously treated with sotorasib and were dose reduced due to toxicity

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