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

NCT ID: NCT04625270

Last Updated: 2025-01-29

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

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

225 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-21

Study Completion Date

2026-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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)

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Low Grade Ovarian Serous Adenocarcinoma Ovarian Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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)

Group Type EXPERIMENTAL

avutometinib (VS-6766)

Intervention Type DRUG

avutometinib (VS-6766) monotherapy

avutometinib (VS-6766) and defactinib

Intervention Type DRUG

avutometinib (VS-6766) and defactinib combination

Part B

To determine the efficacy of the optimal regimen identified from Part A

Group Type EXPERIMENTAL

avutometinib (VS-6766)

Intervention Type DRUG

avutometinib (VS-6766) monotherapy

avutometinib (VS-6766) and defactinib

Intervention Type DRUG

avutometinib (VS-6766) and defactinib combination

Part C:

To evaluate additional efficacy parameters for the optimal regimen identified in Part A.

Group Type EXPERIMENTAL

avutometinib (VS-6766) and defactinib

Intervention Type DRUG

avutometinib (VS-6766) and defactinib combination

Part D

To evaluate additional efficacy parameters for a lower dose of avutometinib in combination with defactinib

Group Type EXPERIMENTAL

avutometinib (VS-6766) and defactinib

Intervention Type DRUG

avutometinib (VS-6766) and defactinib combination

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

avutometinib (VS-6766)

avutometinib (VS-6766) monotherapy

Intervention Type DRUG

avutometinib (VS-6766) and defactinib

avutometinib (VS-6766) and defactinib combination

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

avutometinib (VS-6766) and VS-6063

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

European Network of Gynaecological Oncological Trial Groups (ENGOT)

OTHER

Sponsor Role collaborator

GOG Foundation

NETWORK

Sponsor Role collaborator

Verastem, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Susana Banerjee, MBBS,MA,PhD

Role: PRINCIPAL_INVESTIGATOR

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Rachel Grisham, MD

Role: PRINCIPAL_INVESTIGATOR

GOG Foundation

MD Verastem

Role: STUDY_DIRECTOR

Verastem, Inc.

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Arizona Oncology Associates PC HAL

Scottsdale, Arizona, United States

Site Status

Sansum Clinic

Santa Barbara, California, United States

Site Status

Yale School of Medicine

New Haven, Connecticut, United States

Site Status

Advent Health

Orlando, Florida, United States

Site Status

H. Lee Moffitt Cancer Center and Research Institute - Center for Women's Oncology

Tampa, Florida, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Maryland Oncology and Hematology, P.A.

Glenn Dale, Maryland, United States

Site Status

Minnesota Oncology Hematology PA

Minneapolis, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Cleveland Clinic Women's Health Institute

Cleveland, Ohio, United States

Site Status

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status

University of Oklahoma Medical Center

Oklahoma City, Oklahoma, United States

Site Status

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, United States

Site Status

Northwest Cancer Specialists

Portland, Oregon, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Texas Oncology Austin Central

Austin, Texas, United States

Site Status

Texas Oncology- Dallas Presbyterian Hospital

Dallas, Texas, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

Texas Oncology

Longview, Texas, United States

Site Status

Texas Oncology

McAllen, Texas, United States

Site Status

Texas Oncology

San Antonio, Texas, United States

Site Status

Texas Oncology

The Woodlands, Texas, United States

Site Status

University of Virginia Health System

Charlottesville, Virginia, United States

Site Status

Virginia Cancer Specialists, PC

Gainesville, Virginia, United States

Site Status

UZ Gent Medische Oncologie

Ghent, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

CHU de Liege

Liège, , Belgium

Site Status

Centre de recherche di Centre Hospitalier de i'Universite de Montreal

Montreal, , Canada

Site Status

Princess Margaret Cancer Centre

Toronto, , Canada

Site Status

Hopital Jean Minjoz

Besançon, , France

Site Status

Centre Leon Berard

Lyon, , France

Site Status

ICM - Val d'Aurelle

Montpellier, , France

Site Status

Institut Curie

Paris, , France

Site Status

Insituto Europeo di Oncologia I.R.C.C.S

Milan, , Italy

Site Status

U.O.C. Oncologia 2, Istituto Oncologico Veneto I.R.C.C.S.

Padua, , Italy

Site Status

Hospital Universitario Vall D'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario Reina Sofia

Córdoba, , Spain

Site Status

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Site Status

Western General Hospital

Edinburgh, , United Kingdom

Site Status

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

UCLH Cancer Clinical Trials Unit

London, , United Kingdom

Site Status

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

Royal Marsden Hospital

Sutton, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Belgium Canada France Italy Spain United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Banerjee SN, Van Nieuwenhuysen E, Aghajanian C, D'Hondt V, Monk BJ, Clamp A, Prendergast E, Oaknin A, Ring K, Colombo N, Holloway RW, Rodrigues M, Chon HS, Gourley C, Santin AD, Thaker PH, Gennigens C, Newman G, Salinas E, Youssoufian H, Moore KN, Lustgarten S, O'Malley DM, Van Gorp T, Grisham RN. Efficacy and Safety of Avutometinib +/- Defactinib in Recurrent Low-Grade Serous Ovarian Cancer: Primary Analysis of ENGOT-OV60/GOG-3052/RAMP 201. J Clin Oncol. 2025 Sep;43(25):2782-2792. doi: 10.1200/JCO-25-00112. Epub 2025 Jul 11.

Reference Type DERIVED
PMID: 40644648 (View on PubMed)

McNamara B, Demirkiran C, Hartwich TMP, Bellone S, Manavella D, Mutlu L, Greenman M, Zipponi M, Yang-Hartwich Y, Yang K, Ratner E, Schwartz PE, Coma S, Pachter JA, Santin AD. Preclinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition in low grade serous ovarian cancer. Gynecol Oncol. 2024 Apr;183:133-140. doi: 10.1016/j.ygyno.2024.01.028. Epub 2024 Mar 15.

Reference Type DERIVED
PMID: 38493021 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

GOG-3052

Identifier Type: OTHER

Identifier Source: secondary_id

ENGOT-ov60

Identifier Type: OTHER

Identifier Source: secondary_id

VS-6766-201

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

PARP-inhibition and CTLA-4 Blockade in BRCA-deficient Ovarian Cancer
NCT02571725 ACTIVE_NOT_RECRUITING PHASE1/PHASE2
Selumetinib and Olaparib in Solid Tumors
NCT03162627 ACTIVE_NOT_RECRUITING PHASE1