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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • France
      • Lyon, France, 69373
        • Centre Léon Bérard
      • Marseille, France, 13915
        • Hôpital Nord Marseille
      • Paris, France, 75014
        • Hôpital 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Verastem, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 31, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 29, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 12, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 5, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 6, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 12, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 11, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings