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

Ovarian Cancer Clinical Trial

— RAMP 201  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04625270
• Other study ID #: VS-6766-201
• Secondary ID: GOG-3052ENGOT-ov
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 21, 2020
• Est. completion date: December 2026

Study information

• Verified date: March 2024
• Source: Verastem, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 225
• Est. completion date: December 2026
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Low Grade Ovarian Serous Adenocarcinoma
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• avutometinib (VS-6766)
avutometinib (VS-6766) monotherapy
• avutometinib (VS-6766) and defactinib
avutometinib (VS-6766) and defactinib combination

Locations

Country	Name	City	State
Belgium	UZ Gent Medische Oncologie	Gent
Belgium	UZ Leuven	Leuven
Belgium	CHU de Liege	Liège
Canada	Centre de recherche di Centre Hospitalier de i'Universite de Montreal	Montréal
Canada	Princess Margaret Cancer Centre	Toronto
France	Hopital Jean Minjoz	Besançon
France	Centre Leon Berard	Lyon
France	ICM - Val d'Aurelle	Montpellier
France	Institut Curie	Paris
Italy	Insituto Europeo di Oncologia I.R.C.C.S	Milano
Italy	U.O.C. Oncologia 2, Istituto Oncologico Veneto I.R.C.C.S.	Padova
Spain	Hospital Universitario Vall D'Hebron	Barcelona
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Clínico Universitario de Valencia	Valencia
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	UCLH Cancer Clinical Trials Unit	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Royal Marsden Hospital	Sutton
United States	University of New Mexico Comprehensive Cancer Center	Albuquerque	New Mexico
United States	Texas Oncology Austin Central	Austin	Texas
United States	University of Virginia Health System	Charlottesville	Virginia
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic Women's Health Institute	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Texas Oncology- Dallas Presbyterian Hospital	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Virginia Cancer Specialists, PC	Gainesville	Virginia
United States	Maryland Oncology and Hematology, P.A.	Glenn Dale	Maryland
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Texas Oncology	Longview	Texas
United States	Texas Oncology	McAllen	Texas
United States	Minnesota Oncology Hematology PA	Minneapolis	Minnesota
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Yale School of Medicine	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Oklahoma Medical Center	Oklahoma City	Oklahoma
United States	Advent Health	Orlando	Florida
United States	Northwest Cancer Specialists	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Texas Oncology	San Antonio	Texas
United States	Sansum Clinic	Santa Barbara	California
United States	Arizona Oncology Associates PC HAL	Scottsdale	Arizona
United States	H. Lee Moffitt Cancer Center and Research Institute - Center for Women's Oncology	Tampa	Florida
United States	Texas Oncology	The Woodlands	Texas

Sponsors (3)

Lead Sponsor	Collaborator
Verastem, Inc.	European Network of Gynaecological Oncological Trial Groups (ENGOT), GOG Foundation

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	Overall Response Rate as assessed by Investigator	Proportioned subjects achieving a CR or PR as assess by the investigator	From start of treatment to confirmation of response; 24 weeks
Secondary	Duration of Response (DOR)	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
Secondary	Disease Control Rate (DCR)	CR+PR+stable disease	Greater than or equal to 8 weeks
Secondary	Progression Free Survival (PFS)	From time of first dose of study intervention to PD or death for any cause	Up to 5 years
Secondary	Overall Survival (OS)	From time of first dose of study intervention to death	Up to 5 years