A Study of Avutometinib (VS-6766) V. Avutometinib (VS-6766) + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer with and Without a KRAS Mutation (RAMP 201)

January 26, 2025 updated by: Verastem, Inc.

A Phase 2 Study of Avutometinib (VS-6766) (Dual RAF/MEK Inhibitor) Alone and in Combination with Defactinib (FAK Inhibitor) in Recurrent Low-Grade Serous Ovarian Cancer (LGSOC)

This study will assess the safety and efficacy of avutometinib (VS-6766) monotherapy and in combination with defactinib in subjects with recurrent Low-Grade Serous Ovarian Cancer (LGSOC)

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a multicenter, randomized, open-label Phase 2 study designed to evaluate safety and tolerability and preliminary efficacy of avutometinib (VS-6766) versus avutometinib (VS-6766) in combination with defactinib in subjects with molecularly profiled recurrent LGSOC.

Study Type

Interventional

Enrollment (Estimated)

225

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

  • Belgium
      • Gent, Belgium, 9000
        • UZ Gent Medische Oncologie
      • Leuven, Belgium, 3000
        • UZ Leuven
      • Liège, Belgium, 4000
        • CHU de Liège
  • Canada
      • Montréal, Canada, H2X 0A9
        • Centre de recherche di Centre Hospitalier de i'Universite de Montreal
      • Toronto, Canada, M5G2M9
        • Princess Margaret Cancer Centre
  • France
      • Besançon, France, 2500
        • Hôpital Jean Minjoz
      • Lyon, France, 69008
        • Centre Leon Berard
      • Montpellier, France, 34298
        • ICM - Val d'Aurelle
      • Paris, France, 75248
        • Institut Curie
  • Italy
      • Milano, Italy, 20141
        • Insituto Europeo di Oncologia I.R.C.C.S
      • Padova, Italy, 35128
        • U.O.C. Oncologia 2, Istituto Oncologico Veneto I.R.C.C.S.
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitario Vall d'Hebron
      • Córdoba, Spain, 14004
        • Hospital Universitario Reina Sofia
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
      • Valencia, Spain, 46010
        • Hospital Clinico Universitario de Valencia
  • United Kingdom
      • Edinburgh, United Kingdom, EH4 2XU
        • Western General Hospital
      • Glasgow, United Kingdom, G120YN
        • Beatson West of Scotland Cancer Centre
      • London, United Kingdom, NW1 2PG
        • UCLH Cancer Clinical Trials Unit
      • Manchester, United Kingdom, M20 4BX
        • The Christie NHS Foundation Trust
      • Sutton, United Kingdom
        • Royal Marsden Hospital
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • Arizona Oncology Associates PC HAL
    • California
      • Santa Barbara, California, United States, 93105
        • Sansum Clinic
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale School of Medicine
    • Florida
      • Orlando, Florida, United States, 32804
        • Advent Health
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center and Research Institute - Center for Women's Oncology
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • Maryland
      • Glenn Dale, Maryland, United States, 20769
        • Maryland Oncology and Hematology, P.A.
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Minnesota Oncology Hematology PA
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Nevada
      • Las Vegas, Nevada, United States, 89128
        • Comprehensive Cancer Centers of Nevada
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • University of New Mexico Comprehensive Cancer Center
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Women's Health Institute
      • Columbus, Ohio, United States, 43212
        • The Ohio State University Wexner Medical Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Medical Center
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Willamette Valley Cancer Institute and Research Center
      • Portland, Oregon, United States, 97227
        • Northwest Cancer Specialists
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
    • Texas
      • Austin, Texas, United States, 78731
        • Texas Oncology Austin Central
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center
      • Dallas, Texas, United States, 75231
        • Texas Oncology- Dallas Presbyterian Hospital
      • Longview, Texas, United States, 75601
        • Texas Oncology
      • McAllen, Texas, United States, 78503
        • Texas Oncology
      • San Antonio, Texas, United States, 78240
        • Texas Oncology
      • The Woodlands, Texas, United States, 77380
        • Texas Oncology
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System
      • Gainesville, Virginia, United States, 20155
        • 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:

  • Histologically proven LGSOC (ovarian, peritoneal)
  • Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease.
  • 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, if necessary

Exclusion Criteria:

  • Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy
  • Co-existing high-grade ovarian cancer or another histology
  • History of prior malignancy with recurrence <3 years from the time of enrollment
  • Major surgery within 4 weeks
  • Symptomatic brain metastases requiring steroids or other interventions
  • Known SARS-Cov2 infection (clinical symptoms) ≤28 days prior to first dose of study therapy
  • For subjects with prior MEK exposure, Grade 4 toxicity deemed related to the MEK inhibitor
  • 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
  • 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: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part B
To determine the efficacy of the optimal regimen identified from Part A
Drug: avutometinib (VS-6766)
avutometinib (VS-6766) monotherapy
Drug: avutometinib (VS-6766) and defactinib
avutometinib (VS-6766) and defactinib combination
Other Names:
  • avutometinib (VS-6766) and VS-6063
Experimental: Part A
To determine the optimal regimen, either avutometinib(VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, for subsequent evaluation for efficacy in the Expansion Phase (Part B)
Drug: avutometinib (VS-6766)
avutometinib (VS-6766) monotherapy
Drug: avutometinib (VS-6766) and defactinib
avutometinib (VS-6766) and defactinib combination
Other Names:
  • avutometinib (VS-6766) and VS-6063
Experimental: Part C:
To evaluate additional efficacy parameters for the optimal regimen identified in Part A.
Drug: avutometinib (VS-6766) and defactinib
avutometinib (VS-6766) and defactinib combination
Other Names:
  • avutometinib (VS-6766) and VS-6063
Experimental: Part D
To evaluate additional efficacy parameters for a lower dose of avutometinib in combination with defactinib
Drug: avutometinib (VS-6766) and defactinib
avutometinib (VS-6766) and defactinib combination
Other Names:
  • avutometinib (VS-6766) and VS-6063

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part B: To determine the efficacy of the optimal regimen identified from Part A
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
Part A: Determine optimal regimen of avutometinib (VS-6766) monotherapy or in combination with defactinib
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
Part C: To evaluate additional efficacy parameters for the optimal regimen identified in Part A
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
Part D:To evaluate additional efficacy parameters for a lower dose of avutometinib in combination with defactinib
Time Frame: From start of treatment to confirmation of response; 24 weeks
Confirmed ORR defined according to RECIST 1.1
From start of treatment to confirmation of response; 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate 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
From time of first response to PD as assessed by the BIRC
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+PR+stable disease
Greater than or equal to 8 weeks
Progression Free Survival (PFS)
Time Frame: Up to 5 years
From time of first dose of study intervention to PD or death for any cause
Up to 5 years
Overall Survival (OS)
Time Frame: Up to 5 years
From time of first dose of study intervention to death
Up to 5 years

Collaborators and Investigators

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

Sponsor

Verastem, Inc.

Collaborators

GOG Foundation
European Network of Gynaecological Oncological Trial Groups (ENGOT)

Investigators

  • Principal Investigator: Susana Banerjee, MBBS,MA,PhD, European Network of Gynaecological Oncological Trial Groups (ENGOT)
  • Principal Investigator: Rachel Grisham, MD, GOG Foundation
  • Study Director: MD Verastem, Verastem, Inc.

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 21, 2020

Primary Completion (Actual)

November 15, 2024

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

November 5, 2020

First Submitted That Met QC Criteria

November 6, 2020

First Posted (Actual)

November 12, 2020

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 26, 2025

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VS-6766-201
  • GOG-3052 (Other Identifier: The GOG Foundation, Inc.)
  • ENGOT-ov60 (Other Identifier: ENGOT)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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