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

NCT04620330 | Completed Phase 2 FDA Drug

• 1 other identifier: VS-6766-202
• Study Type: interventional
• Target: 90
• Locations: 5 countries
• Sites: 45

Brief Summary

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.

Conditions

Non Small Cell Lung Cancer; KRAS Activating Mutation

Keywords

NSCLC; KRAS-G12V; G12V; BRAF; V600E; KRAS

Outcome Measures

Primary Outcomes (4)

• To determine the optimal regimen, either avutometinib (VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, in KRAS-G12V NSCLC

  Confirmed overall response rate per RECIST 1.1

  From start of treatment to confirmation of response; 24 weeks

• To evaluate the initial efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC

  Confirmed overall response rate per RECIST 1.1

  From start of treatment to confirmation of response; 24 weeks

• To determine efficacy in KRAS-other (non-G12V) NSCLC

  Confirmed overall response rate per RECIST 1.1

  From start of treatment to confirmation of response; 24 weeks

• To determine the efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC

  Confirmed overall response rate per RECIST 1.1

  From start of treatment to confirmation of response; 24 weeks

Secondary Outcomes (6)

• To characterize the safety and toxicity profile of VS-6766 as a monotherapy and in combination with defactinib in KRAS-MT NSCLC and in BRAF-MT NSCLC

  24 weeks

• Overall Response Rate per RECIST 1.1 as assessed by Investigator

  From start of treatment to confirmation of response; 24 weeks

• Duration of Response (DOR)

  Time from the first documentation of response to first documentation of progressive disease or death due to any cause, greater than or equal to 6 months

• Disease Control Rate (DCR)

  Greater than or equal to 8 weeks

• Progression Free Survival (PFS)

  Up to 5 years

Study Arms (5)

Arm 1: avutometinib (VS-6766) monotherapy

EXPERIMENTAL

in patients with NSCLC KRAS-G12V tumor

Drug: avutometinib (VS-6766)

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

EXPERIMENTAL

in patients with a NSCLC KRAS-G12V tumor

Drug: avutometinib (VS-6766) and Defactinib

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

EXPERIMENTAL

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

Drug: avutometinib (VS-6766) and Defactinib

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

EXPERIMENTAL

in patients with a NSCLC BRAF-V600E tumor

Drug: avutometinib (VS-6766) and Defactinib

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

EXPERIMENTAL

in patients with a NSCLC BRAF-non-V600E tumor

Drug: avutometinib (VS-6766) and Defactinib

Interventions

avutometinib (VS-6766) DRUG

Monotherapy

Arm 1: avutometinib (VS-6766) monotherapy

avutometinib (VS-6766) and Defactinib DRUG

Combination therapy

Also known as: avutometinib (VS-6766) and VS-6063

Arm 2: avutometinib (VS-6766) in combination with defactinib; Arm 3: avutometinib (VS-6766) in combination with defactinib; Arm 4: avutometinib (VS-6766) in combination with defactinib; Arm 5:avutometinib (VS-6766) in combination with defactinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Verastem, Inc.: lead

Study Sites (45)

City of Hope

Duarte, California, 91010, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Cancer Centers

Lone Tree, Colorado, 80124, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33908, United States

Location

Florida Cancer Specialists

St. Petersburg, Florida, 33705, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Medical Center-Duchossois Center for Advanced Medicine

Chicago, Illinois, 60637, United States

Location

Illinois Cancer Specialists

Niles, Illinois, 60714, United States

Location

Hematology/Oncology Clinic, LLP

Baton Rouge, Louisiana, 70809, United States

Location

Maryland Oncology Hematology P.A

Columbia, Maryland, 21044, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Cancer Institute/Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Northwell Health-Monter Cancer Center

Lake Success, New York, 11042, United States

Location

Zangmeister Cancer Center

Columbus, Ohio, 43219, United States

Location

Northwest Cancer Specialists, P.C.

Portland, Oregon, 97213, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Univ. of Pittsburgh Med Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Chattanooga Oncology Hematology Assoc.

Chattanooga, Tennessee, 037404, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Texas Oncology

Dallas, Texas, 75246, United States

Location

Texas Oncology Ft Worth Cancer Center

Fort Worth, Texas, 76104, United States

Location

Texas Oncology

Grapevine, Texas, 76051, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Centre Leon Berard

Lyon, 69373, France

Location

Hopital Nord Marseille

Marseille, 13915, France

Location

Hopital Cochin

Paris, 75014, France

Location

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

Saint-Herblain, 44805, France

Location

Cancerologie Gustave Roussy - Cancer Medicine

Villejuif, 94800, France

Location

Klinikum Chemnitz gGmbH

Chemnitz, 09116, Germany

Location

Universitatsklinkum Leipzig

Leipzig, 04103, Germany

Location

Evangelisches Klinkum Bethel

Straße, 33611, Germany

Location

Azienda Ospedaliera Universitaria

Orbassano, Torino, 10043, Italy

Location

Irccs, Irts

Meldola, 47014, Italy

Location

UOC di Oncologia Medica

Parma, 43126, Italy

Location

Centro Ricerche Cliniche di Verona

Verona, 37134, Italy

Location

Complejo Hospitalario Universiario a Coruna Teresa

A Coruña, 15006, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital 12 de Octubre

Córdoba, 28041, Spain

Location

Universitario de Teatinos

Málaga, 29010, Spain

Location

Hospital Universitario Virgen de la Macarena

Seville, 41009, Spain

Location

Related Publications (1)

• 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.

  PMID: 35285277 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

defactinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Ross Camidge, MD, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

• MD Verastem

  Verastem, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2020
• First Posted: November 6, 2020
• Study Start: December 31, 2020
• Primary Completion: August 29, 2023
• Study Completion: December 12, 2023
• Last Updated: January 12, 2024

Record last verified: 2024-01

Locations

IT (4); US (28); FR (5); DE (3); ES (5)