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

NCT04625270 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: VS-6766-201GOG-3052ENGOT-ov60
• Study Type: interventional
• Target: 225
• Locations: 7 countries
• Sites: 47

Brief Summary

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)

Conditions

Low Grade Ovarian Serous Adenocarcinoma; Ovarian Cancer

Keywords

Low Grade Serous Ovarian Cancer; KRAS, KRAS wt

Outcome Measures

Primary Outcomes (4)

• Part A: Determine optimal regimen of avutometinib (VS-6766) monotherapy or in combination with defactinib

  Confirmed overall response rate per RECIST 1.1

  From start of treatment to confirmation of response; 24 weeks

• Part B: To determine the efficacy of the optimal regimen identified from Part A

  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

  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

  Confirmed ORR defined according to RECIST 1.1

  From start of treatment to confirmation of response; 24 weeks

Secondary Outcomes (5)

• Overall Response Rate 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

• Overall Survival (OS)

  Up to 5 years

Study Arms (4)

Part A

EXPERIMENTAL

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); Drug: avutometinib (VS-6766) and defactinib

Part B

EXPERIMENTAL

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

Drug: avutometinib (VS-6766); Drug: avutometinib (VS-6766) and defactinib

Part C:

EXPERIMENTAL

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

Drug: avutometinib (VS-6766) and defactinib

Part D

EXPERIMENTAL

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

Drug: avutometinib (VS-6766) and defactinib

Interventions

avutometinib (VS-6766) DRUG

avutometinib (VS-6766) monotherapy

Part A; Part B

avutometinib (VS-6766) and defactinib DRUG

avutometinib (VS-6766) and defactinib combination

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

Part A; Part B; Part C:; Part D

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Verastem, Inc.: lead
• European Network of Gynaecological Oncological Trial Groups (ENGOT): collaborator
• GOG Foundation: collaborator

Study Sites (47)

Arizona Oncology Associates PC HAL

Scottsdale, Arizona, 85258, United States

Location

Sansum Clinic

Santa Barbara, California, 93105, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

Advent Health

Orlando, Florida, 32804, United States

Location

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

Tampa, Florida, 33612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Maryland Oncology and Hematology, P.A.

Glenn Dale, Maryland, 20769, United States

Location

Minnesota Oncology Hematology PA

Minneapolis, Minnesota, 55404, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89128, United States

Location

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cleveland Clinic Women's Health Institute

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43212, United States

Location

University of Oklahoma Medical Center

Oklahoma City, Oklahoma, 73104, United States

Location

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, 97401, United States

Location

Northwest Cancer Specialists

Portland, Oregon, 97227, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Texas Oncology Austin Central

Austin, Texas, 78731, United States

Location

Texas Oncology- Dallas Presbyterian Hospital

Dallas, Texas, 75231, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Texas Oncology

Longview, Texas, 75601, United States

Location

Texas Oncology

McAllen, Texas, 78503, United States

Location

Texas Oncology

San Antonio, Texas, 78240, United States

Location

Texas Oncology

The Woodlands, Texas, 77380, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Virginia Cancer Specialists, PC

Gainesville, Virginia, 20155, United States

Location

UZ Gent Medische Oncologie

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

CHU de Liege

Liège, 4000, Belgium

Location

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

Montreal, H2X 0A9, Canada

Location

Princess Margaret Cancer Centre

Toronto, M5G2M9, Canada

Location

Hopital Jean Minjoz

Besançon, 2500, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

ICM - Val d'Aurelle

Montpellier, 34298, France

Location

Institut Curie

Paris, 75248, France

Location

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

Milan, 20141, Italy

Location

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

Padua, 35128, Italy

Location

Hospital Universitario Vall D'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G120YN, United Kingdom

Location

UCLH Cancer Clinical Trials Unit

London, NW1 2PG, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Royal Marsden Hospital

Sutton, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 40644648 DERIVED

• 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.

  PMID: 38493021 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

defactinib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Susana Banerjee, MBBS,MA,PhD

  European Network of Gynaecological Oncological Trial Groups (ENGOT)

  PRINCIPAL INVESTIGATOR

• Rachel Grisham, MD

  GOG Foundation

  PRINCIPAL INVESTIGATOR

• MD Verastem

  Verastem, Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: November 5, 2020
• First Posted: November 12, 2020
• Study Start: December 21, 2020
• Primary Completion: November 15, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 29, 2025

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4); CA (2); BE (3); IT (2); ES (4); GB (5); US (27)