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

NCT ID: NCT05074810

Last Updated: 2026-01-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

153 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-12

Study Completion Date

2027-04-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Non Small Cell Lung Cancer KRAS Activating Mutation

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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avutometinib (VS-6766)+sotorasib

To determine the recommended phase 2 dose (RP2D) for avutometinib (VS 6766) in combination with sotorasib in KRAS G12C inhibitor naïve and exposed patients

Group Type EXPERIMENTAL

avutometinib and sotorasib

Intervention Type DRUG

The RP2D of avutometinib + sotorasib determined in Part A will be used in Part B dose expansion

avutometinib (VS-6766)+sotorasib - KRAS G12C inhibitor naïve

To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor naïve patients

Group Type EXPERIMENTAL

avutometinib and sotorasib

Intervention Type DRUG

The RP2D of avutometinib + sotorasib determined in Part A will be used in Part B dose expansion

avutometinib (VS-6766)+sotorasib - KRAS G12C inhibitor exposed

To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor exposed patients

Group Type EXPERIMENTAL

avutometinib and sotorasib

Intervention Type DRUG

The RP2D of avutometinib + sotorasib determined in Part A will be used in Part B dose expansion

avutometinib (VS-6766)+sotorasib+defactinib

To determine the recommended phase 2 dose (RP2D) for avutometinib (VS-6766) in combination with sotorasib and defactinib in KRAS G12C inhibitor exposed patients

Group Type EXPERIMENTAL

avutometinib and sotorasib and defactinib

Intervention Type DRUG

The RP2D of avutometinib + sotorasib + defactinib determined in Part A will be used in Part B dose expansion

avutometinib (VS-6766)+sotorasib+defactinib - KRAS G12C inhibitor naive

To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor naïve patients

Group Type EXPERIMENTAL

avutometinib and sotorasib and defactinib

Intervention Type DRUG

The RP2D of avutometinib + sotorasib + defactinib determined in Part A will be used in Part B dose expansion

avutometinib (VS-6766)+sotorasib+defactinib - KRAS G12C inhibitor exposed

To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor exposed patients

Group Type EXPERIMENTAL

avutometinib and sotorasib and defactinib

Intervention Type DRUG

The RP2D of avutometinib + sotorasib + defactinib determined in Part A will be used in Part B dose expansion

Interventions

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avutometinib and sotorasib

The RP2D of avutometinib + sotorasib determined in Part A will be used in Part B dose expansion

Intervention Type DRUG

avutometinib and sotorasib and defactinib

The RP2D of avutometinib + sotorasib + defactinib determined in Part A will be used in Part B dose expansion

Intervention Type DRUG

Other Intervention Names

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AMG 510 LUMAKRAS™ VS-6766 AMG 510 LUMAKRAS™ VS-6766 VS-6063

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role collaborator

Verastem, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD Verastem

Role: STUDY_DIRECTOR

Verastem, Inc.

Locations

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Rocky Mountain Cancer Center, LLP

Boulder, Colorado, United States

Site Status

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

MedStar Washington Hospital Center, MedStar Georgetown Cancer Institute,

Washington D.C., District of Columbia, United States

Site Status

Illinois Cancer Specialists

Arlington Heights, Illinois, United States

Site Status

Maryland Oncology & Hematology, P.A.

Rockville, Maryland, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Minnesota Oncology Hematology, P.A

Woodbury, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Ohio State University Brain and Spine Hospital

Columbus, Ohio, United States

Site Status

Consultants in Medical Oncology & Hematology

Broomall, Pennsylvania, United States

Site Status

Alliance Cancer Specialists,

Horsham, Pennsylvania, United States

Site Status

Texas Oncology

Austin, Texas, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Texas Oncology - Fort Worth Cancer Center

Fort Worth, Texas, United States

Site Status

Texas Oncology

Longview, Texas, United States

Site Status

Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care

Blacksburg, Virginia, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Northwest Cancer Specialists

Vancouver, Washington, United States

Site Status

University Hospital Gent

Ghent, , Belgium

Site Status

CHU de Liège

Liège, , Belgium

Site Status

CHRU of Lille

Lille, , France

Site Status

Hôpital Cochin

Paris, , France

Site Status

Hôpital Foch

Suresnes, , France

Site Status

Leids Universitair Medisch Centrum

Leiden, , Netherlands

Site Status

Erasmus MC

Rotterdam, , Netherlands

Site Status

Hospital Teresa Herrera (C.H.U.A.C)

A Coruña, , Spain

Site Status

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Site Status

Hospital Universitario Fundación Jiménez Díaz

Madrid, , Spain

Site Status

Hospital Universitario Virgen De La Victoria

Málaga, , Spain

Site Status

Hospital Universitario Virgen de la Macarena

Seville, , Spain

Site Status

University of Leicester

Leicester, , United Kingdom

Site Status

Royal Marsden Hospital

London, , United Kingdom

Site Status

Royal Marsden Hospital

Sutton, , United Kingdom

Site Status

Countries

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United States Belgium France Netherlands Spain United Kingdom

Other Identifiers

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VS-6766-203

Identifier Type: -

Identifier Source: org_study_id

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