A Study of Avutometinib (VS-6766) + Defactinib in Recurrent KRAS G12V, Other KRAS and BRAF Non-Small Cell Lung Cancer (RAMP202)

January 11, 2024 updated by: Verastem, Inc.

A Phase 2 Study of Avutometinib (VS-6766) (Dual RAF/MEK Inhibitor) as a Single Agent and In Combination With Defactinib (FAK Inhibitor) in Recurrent KRAS-Mutant (KRAS-MT) and BRAF-Mutant (BRAF-MT) Non-Small Cell Lung Cancer (NSCLC) (RAMP 202)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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).

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lyon, France, 69373
        • Centre Léon Bérard
      • Marseille, France, 13915
        • Hopital Nord Marseille
      • Paris, France, 75014
        • Hopital Cochin
      • Saint-Herblain, France, 44805
        • Institute De Cancerologie De L'Ouest Site Paul Papin Oncologie Medicale
      • Villejuif, France, 94800
        • Cancerologie Gustave Roussy - Cancer Medicine
  • Germany
      • Chemnitz, Germany, 09116
        • Klinikum Chemnitz gGmbH
      • Leipzig, Germany, 04103
        • Universitatsklinkum Leipzig
      • Straße, Germany, 33611
        • Evangelisches Klinkum Bethel
  • Italy
      • Meldola, Italy, 47014
        • Irccs, Irts
      • Parma, Italy, 43126
        • UOC di Oncologia Medica
      • Verona, Italy, 37134
        • Centro Ricerche Cliniche di Verona
    • Torino
      • Orbassano, Torino, Italy, 10043
        • Azienda Ospedaliera Universitaria
  • Spain
      • Barcelona, Spain
        • Hospital Clinic de Barcelona
      • Coruña, Spain, 15006
        • Complejo Hospitalario Universiario a Coruna Teresa
      • Córdoba, Spain, 28041
        • Hospital 12 de Octubre
      • Málaga, Spain, 29010
        • Universitario de Teatinos
      • Sevilla, Spain, 41009
        • Hospital Universitario Virgen de la Macarena
  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Hospital
      • Lone Tree, Colorado, United States, 80124
        • Rocky Mountain Cancer Centers
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University Medical Center
    • Florida
      • Fort Myers, Florida, United States, 33908
        • Florida Cancer Specialists
      • Saint Petersburg, Florida, United States, 33705
        • Florida Cancer Specialists
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University School of Medicine
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center-Duchossois Center for Advanced Medicine
      • Niles, Illinois, United States, 60714
        • Illinois Cancer Specialists
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70809
        • Hematology/Oncology Clinic, LLP
    • Maryland
      • Columbia, Maryland, United States, 21044
        • Maryland Oncology Hematology P.A
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Cancer Institute/Henry Ford Health System
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • Lake Success, New York, United States, 11042
        • Northwell Health-Monter Cancer Center
    • Ohio
      • Columbus, Ohio, United States, 43219
        • Zangmeister Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97213
        • Northwest Cancer Specialists, P.C.
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Pittsburgh, Pennsylvania, United States, 15232
        • Univ. of Pittsburgh Med Center
    • Tennessee
      • Chattanooga, Tennessee, United States, 037404
        • Chattanooga Oncology Hematology Assoc.
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology
    • Texas
      • Dallas, Texas, United States, 75246
        • Texas Oncology
      • Fort Worth, Texas, United States, 76104
        • Texas Oncology Ft Worth Cancer Center
      • Grapevine, Texas, United States, 76051
        • Texas Oncology
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists, PC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1: avutometinib (VS-6766) monotherapy
in patients with NSCLC KRAS-G12V tumor
Drug: avutometinib (VS-6766)
Monotherapy
Experimental: Arm 2: avutometinib (VS-6766) in combination with defactinib
in patients with a NSCLC KRAS-G12V tumor
Drug: avutometinib (VS-6766) and Defactinib
Combination therapy
Other Names:
  • avutometinib (VS-6766) and VS-6063
Experimental: Arm 3: avutometinib (VS-6766) in combination with defactinib
in patients with a NSCLC KRAS-other (non-G12V) tumor
Drug: avutometinib (VS-6766) and Defactinib
Combination therapy
Other Names:
  • avutometinib (VS-6766) and VS-6063
Experimental: Arm 4: avutometinib (VS-6766) in combination with defactinib
in patients with a NSCLC BRAF-V600E tumor
Drug: avutometinib (VS-6766) and Defactinib
Combination therapy
Other Names:
  • avutometinib (VS-6766) and VS-6063
Experimental: Arm 5:avutometinib (VS-6766) in combination with defactinib
in patients with a NSCLC BRAF-non-V600E tumor
Drug: avutometinib (VS-6766) and Defactinib
Combination therapy
Other Names:
  • avutometinib (VS-6766) and VS-6063

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To determine efficacy in KRAS-other (non-G12V) NSCLC
Time Frame: From start of treatment to confirmation of response; 24 weeks
Confirmed overall response rate per RECIST 1.1
From start of treatment to confirmation of response; 24 weeks
To determine the optimal regimen, either avutometinib (VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, in KRAS-G12V NSCLC
Time Frame: From start of treatment to confirmation of response; 24 weeks
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
Time Frame: From start of treatment to confirmation of response; 24 weeks
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
Time Frame: From start of treatment to confirmation of response; 24 weeks
Confirmed overall response rate per RECIST 1.1
From start of treatment to confirmation of response; 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Up to 5 years
From time of first dose of study intervention to death
Up to 5 years
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
Time Frame: 24 weeks
Adverse events (AEs), serious AEs (SAEs), vital signs, physical examinations, clinical laboratory values, and tolerability (dose interruptions/reductions)
24 weeks
Overall Response Rate per RECIST 1.1 as assessed by Investigator
Time Frame: From start of treatment to confirmation of response; 24 weeks
Proportioned subjects achieving a CR or PR as assess by the investigator
From start of treatment to confirmation of response; 24 weeks
Duration of Response (DOR)
Time Frame: 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
Time of first response to PD as assessed by the IRC
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)
Time Frame: Greater than or equal to 8 weeks
CR and PR stable disease as assessed by the IRC
Greater than or equal to 8 weeks
Progression Free Survival (PFS)
Time Frame: Up to 5 years
From the time of first dose of study intervention to PD or death from any cause
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Verastem, Inc.

Investigators

  • Principal Investigator: Ross Camidge, MD, PhD, University of Colorado, Denver
  • Study Director: MD Verastem, Verastem, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 31, 2020

Primary Completion (Actual)

August 29, 2023

Study Completion (Actual)

December 12, 2023

Study Registration Dates

First Submitted

November 5, 2020

First Submitted That Met QC Criteria

November 5, 2020

First Posted (Actual)

November 6, 2020

Study Record Updates

Last Update Posted (Actual)

January 12, 2024

Last Update Submitted That Met QC Criteria

January 11, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VS-6766-202

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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