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Combination treatment for KRAS G12C Non-Small Cell Lung Cancer

A Phase 1/2 Study of Avutometinib (VS-6766) in Combination With Sotorasib With or Without Defactinib in Patients With KRAS G12C Mutant Non-Small Cell Lung Cancer (NSCLC)

PHASE1; PHASE2 · Verastem, Inc. · NCT05074810

This study is testing a new combination of drugs to see if they can help people with a specific type of lung cancer called KRAS G12C mutant Non-Small Cell Lung Cancer feel better and manage their condition.

Quick facts

PhasePHASE1; PHASE2
Study typeInterventional
Enrollment153 (estimated)
Ages18 Years and up
SexAll
SponsorVerastem, Inc. (industry)
Drugs / interventionsavutometinib, defactinib
Locations34 sites (Boulder, Colorado and 33 other locations)
Trial IDNCT05074810 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of a combination of avutometinib (VS-6766) and sotorasib, with or without defactinib, in patients with KRAS G12C mutant Non-Small Cell Lung Cancer (NSCLC). It is a multicenter, non-randomized, open-label Phase 1/2 study that includes patients who have previously been treated with a G12C inhibitor as well as those who have not. The study aims to determine the tolerability and effectiveness of these drug combinations in managing this specific type of lung cancer.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed KRAS G12C mutant NSCLC who have received prior systemic treatment.

Not a fit: Patients who have not been diagnosed with KRAS G12C mutation or those who have received systemic anti-cancer therapy within 4 weeks prior to the study may not benefit.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with KRAS G12C NSCLC, potentially improving their outcomes.

How similar studies have performed: Other studies have shown promising results with similar combinations targeting KRAS mutations, indicating potential for success.

Eligibility criteria

Show full inclusion / exclusion 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

Where this trial is running

Boulder, Colorado and 33 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Non Small Cell Lung Cancer, KRAS Activating Mutation, NSCLC, KRAS G12C

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.