A Study of Avutometinib (VS-6766) + Defactinib in Recurrent KRAS G12V, Other KRAS and BRAF Non-Small Cell Lung Cancer

NCT ID: NCT04620330

Last Updated: 2024-01-12

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

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-31

Study Completion Date

2023-12-12

Brief Summary

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This study will assess the safety and efficacy of avutometinib (VS-6766) monotherapy or VS-6766 in combination with defactinib in subjects with recurrent Non-small cell lung cancer.

Detailed Description

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This is a multicenter, open-label Phase 2 study designed to evaluate safety and tolerability and efficacy of avutometinib (VS-6766) versus avutometinib (VS-6766) in combination with defactinib in subjects with KRAS and BRAF mutant NSCLC following treatment with an appropriate platinum-based regimen and an approved immune checkpoint inhibitor (CPI).

Conditions

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Non Small Cell Lung Cancer KRAS Activating Mutation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1: avutometinib (VS-6766) monotherapy

in patients with NSCLC KRAS-G12V tumor

Group Type EXPERIMENTAL

avutometinib (VS-6766)

Intervention Type DRUG

Monotherapy

Arm 2: avutometinib (VS-6766) in combination with defactinib

in patients with a NSCLC KRAS-G12V tumor

Group Type EXPERIMENTAL

avutometinib (VS-6766) and Defactinib

Intervention Type DRUG

Combination therapy

Arm 3: avutometinib (VS-6766) in combination with defactinib

in patients with a NSCLC KRAS-other (non-G12V) tumor

Group Type EXPERIMENTAL

avutometinib (VS-6766) and Defactinib

Intervention Type DRUG

Combination therapy

Arm 4: avutometinib (VS-6766) in combination with defactinib

in patients with a NSCLC BRAF-V600E tumor

Group Type EXPERIMENTAL

avutometinib (VS-6766) and Defactinib

Intervention Type DRUG

Combination therapy

Arm 5:avutometinib (VS-6766) in combination with defactinib

in patients with a NSCLC BRAF-non-V600E tumor

Group Type EXPERIMENTAL

avutometinib (VS-6766) and Defactinib

Intervention Type DRUG

Combination therapy

Interventions

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avutometinib (VS-6766)

Monotherapy

Intervention Type DRUG

avutometinib (VS-6766) and Defactinib

Combination therapy

Intervention Type DRUG

Other Intervention Names

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avutometinib (VS-6766) and VS-6063

Eligibility Criteria

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Inclusion Criteria

* Male or female subjects ≥ 18 years of age
* Histologic or cytologic evidence of NSCLC
* Known KRAS or BRAF mutation
* The subject must have received appropriate prior therapy
* 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 (excluding placement of vascular access)
* History of treatment with a direct and specific inhibitor of MEK, KRAS or BRAF except for treatment of BRAF V-600E mutant NSCLC
* Exposure to strong CYP2C9 and CYP3A4 inhibitors or inducers within 7 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
* Active skin disorder that has required systemic therapy within the past 1 year
* History of rhabdomyolysis
* Concurrent ocular disorders
* Concurrent heart disease or severe obstructive pulmonary disease
* Subjects with the inability to swallow oral medications
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Verastem, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ross Camidge, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

MD Verastem

Role: STUDY_DIRECTOR

Verastem, Inc.

Locations

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City of Hope

Duarte, California, United States

Site Status

University of Colorado Hospital

Aurora, Colorado, United States

Site Status

Rocky Mountain Cancer Centers

Lone Tree, Colorado, United States

Site Status

Georgetown University Medical Center

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

Site Status

Florida Cancer Specialists

Fort Myers, Florida, United States

Site Status

Florida Cancer Specialists

St. Petersburg, Florida, United States

Site Status

Emory University School of Medicine

Atlanta, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Chicago Medical Center-Duchossois Center for Advanced Medicine

Chicago, Illinois, United States

Site Status

Illinois Cancer Specialists

Niles, Illinois, United States

Site Status

Hematology/Oncology Clinic, LLP

Baton Rouge, Louisiana, United States

Site Status

Maryland Oncology Hematology P.A

Columbia, Maryland, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Henry Ford Cancer Institute/Henry Ford Health System

Detroit, Michigan, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Northwell Health-Monter Cancer Center

Lake Success, New York, United States

Site Status

Zangmeister Cancer Center

Columbus, Ohio, United States

Site Status

Northwest Cancer Specialists, P.C.

Portland, Oregon, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Univ. of Pittsburgh Med Center

Pittsburgh, Pennsylvania, United States

Site Status

Chattanooga Oncology Hematology Assoc.

Chattanooga, Tennessee, United States

Site Status

Tennessee Oncology

Nashville, Tennessee, United States

Site Status

Texas Oncology

Dallas, Texas, United States

Site Status

Texas Oncology Ft Worth Cancer Center

Fort Worth, Texas, United States

Site Status

Texas Oncology

Grapevine, Texas, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Centre Leon Berard

Lyon, , France

Site Status

Hopital Nord Marseille

Marseille, , France

Site Status

Hopital Cochin

Paris, , France

Site Status

Institute De Cancerologie De L'Ouest Site Paul Papin Oncologie Medicale

Saint-Herblain, , France

Site Status

Cancerologie Gustave Roussy - Cancer Medicine

Villejuif, , France

Site Status

Klinikum Chemnitz gGmbH

Chemnitz, , Germany

Site Status

Universitatsklinkum Leipzig

Leipzig, , Germany

Site Status

Evangelisches Klinkum Bethel

Straße, , Germany

Site Status

Azienda Ospedaliera Universitaria

Orbassano, Torino, Italy

Site Status

Irccs, Irts

Meldola, , Italy

Site Status

UOC di Oncologia Medica

Parma, , Italy

Site Status

Centro Ricerche Cliniche di Verona

Verona, , Italy

Site Status

Complejo Hospitalario Universiario a Coruna Teresa

A Coruña, , Spain

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Hospital 12 de Octubre

Córdoba, , Spain

Site Status

Universitario de Teatinos

Málaga, , Spain

Site Status

Hospital Universitario Virgen de la Macarena

Seville, , Spain

Site Status

Countries

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United States France Germany Italy Spain

References

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Capelletto E, Bironzo P, Denis L, Koustenis A, Bungaro M, Novello S. Single agent VS-6766 or VS-6766 plus defactinib in KRAS-mutant non-small-cell lung cancer: the RAMP-202 phase II trial. Future Oncol. 2022 May;18(16):1907-1915. doi: 10.2217/fon-2021-1582. Epub 2022 Mar 14.

Reference Type DERIVED
PMID: 35285277 (View on PubMed)

Other Identifiers

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VS-6766-202

Identifier Type: -

Identifier Source: org_study_id

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