A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer
RAMP 301
A Phase 3, Randomized, Open-Label Study of Combination Therapy With Avutometinib Plus Defactinib Versus Investigator's Choice of Treatment in Patients With Recurrent Low-Grade Serous Ovarian Cancer (LGSOC) (RAMP 301)
3 other identifiers
interventional
270
16 countries
106
Brief Summary
This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with defactinib versus Investigator's choice of treatments (ICT) in subjects with recurrent LGSOC who have progressed on a prior platinum-based therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Mar 2024
Longer than P75 for phase_3
106 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 2, 2023
CompletedFirst Posted
Study publicly available on registry
October 10, 2023
CompletedStudy Start
First participant enrolled
March 18, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 15, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 9, 2031
July 31, 2026
July 1, 2026
4.6 years
October 2, 2023
July 29, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS) per blinded independent central review (BICR)
Progression-free survival (PFS) according to RECIST version 1.1, per blinded independent central review (BICR)
Up to 24 months
Secondary Outcomes (11)
Overall Survival (OS)
Up to 5 years
Progression Free Survival (PFS) per investigator assessment
24 months
Objective response rate (ORR)
12 months
Duration of Response (DOR)
12 months
Disease Control Rate (DCR)
6 months
- +6 more secondary outcomes
Study Arms (2)
avutometinib + defactinib
EXPERIMENTALAvutometinib 3.2 mg, PO, twice weekly for 21 days on, 7 days off in a 28-day (4 weeks) cycle in combination with defactinib 200 mg, PO, twice daily for 21 days on, 7 days off in a 28-day(4 week) cycle.
Investigator Choice of Treatment (ICT)
ACTIVE COMPARATORPatients will receive one of the following therapies as determined by the Investigator: * Pegylated liposomal doxorubicin: 40 mg/m2 IV on Day 1 of each 28-day (4 week) cycle. * Paclitaxel: 80 mg/m2 IV on Days 1, 8, and 15 of each 28-day (4 week) cycle. * Anastrozole: 1 mg, PO, once daily of each 28-day (4 week) cycle. * Letrozole: 2.5 mg, PO, once daily of each 28-day (4 week) cycle.
Interventions
Avutometinib: administered orally
Defactinib: administered orally
administered intravenously
administered intravenously
Eligibility Criteria
You may qualify if:
- Histologically proven LGSOC (ovarian, fallopian, peritoneal)
- Documented mutational status of KRAS by a validated tumor-tissue based diagnostic test.
- Suitable for treatment with at least one of the Investigator's Choice of Treatments:pegylated liposomal doxorubicin, paclitaxel, letrozole, anastrozole.
- Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease.
- Measurable disease according to RECIST v1.1.
- An Eastern Cooperative Group (ECOG) performance status ≤ 1.
- Adequate organ function.
- Adequate recovery from toxicities related to prior treatments.
- For patients with reproductive potential, a negative pregnancy test must be confirmed and agreement to use highly effective method of contraceptive.
- Willingness to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
You may not qualify if:
- Patients will be excluded from the study if they meet any of the following criteria:
- Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy.
- Co-existing high-grade serous ovarian cancer or mixed histology.
- Prior treatment with avutometinib, defactinib, or other FAK inhibitors.
- History of prior malignancy with recurrence \<3 years from the time of enrollment.
- Major surgery within 4 weeks, minor surgery within 1 week, or palliative radiotherapy within 1 week of the first dose of study intervention.
- Symptomatic brain metastases requiring steroids or other interventions, known leptomeningeal metastases, or spinal cord compression.
- An active skin disorder that has required systemic therapy within one year of the first dose of study intervention.
- History of medically significant rhabdomyolysis.
- For subjects with prior MEK or RAF exposure, Grade 4 toxicity is deemed related to the MEK inhibitor.
- Symptomatic bowel obstruction within 3 months of the first dose of study intervention
- Concurrent ocular disorders.
- Concurrent heart disease or severe obstructive pulmonary disease.
- Active or past medical history of interstitial lung disease/pneumonitis, including drug-induced or radiation pneumonitis, pulmonary fibrosis, or adult respiratory distress syndrome (ARDS).
- Subjects with the inability to swallow oral medications.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Verastem, Inc.lead
- GOG Foundationcollaborator
- Australia New Zealand Gynaecological Oncology Groupcollaborator
- Korean Gynecologic Oncology Groupcollaborator
- European Network of Gynaecological Oncological Trial Groups (ENGOT)collaborator
Study Sites (106)
HonorHealth
Phoenix, Arizona, 85016, United States
University of Arkansas
Little Rock, Arkansas, 72205, United States
UCLA Health
Los Angeles, California, 90095, United States
UC Davis
Sacramento, California, 95817, United States
University of California, San Francisco
San Francisco, California, 94143, United States
Yale University
New Haven, Connecticut, 06520, United States
Florida Cancer Specialists - South
Fort Myers, Florida, 33901, United States
Mount Sinai
Miami Beach, Florida, 33140, United States
AdventHealth
Orlando, Florida, 32804, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Florida Cancer Specialists Research East
West Palm Beach, Florida, 33401, United States
Winship Cancer Institute at Emory University
Atlanta, Georgia, 30322, United States
NorthShore University HealthSystem
Evanston, Illinois, 60201, United States
Louisiana State University
New Orleans, Louisiana, 70112, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21287, United States
Karmanos Cancer Center
Detroit, Michigan, 48201, United States
Minnesota Oncology Hematology
Minneapolis, Minnesota, 55404, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Atrium Health
Charlotte, North Carolina, 28203, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Ohio State
Hilliard, Ohio, 43026, United States
University of Oklahoma Medical Center
Oklahoma City, Oklahoma, 73104, United States
Willamette Valley Cancer Institute
Eugene, Oregon, 97401, United States
Northwest Cancer Specialists
Portland, Oregon, 97227, United States
Asplundh Cancer Pavilion | Jefferson Health
Philadelphia, Pennsylvania, 19090, United States
Allegheny Health Network
Pittsburgh, Pennsylvania, 15224, United States
Texas Oncology Central
Austin, Texas, 78731, United States
Texas Oncology-Fort Worth Cancer Center
Fort Worth, Texas, 76104, United States
Houston Methodist
Houston, Texas, 77030, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Texas Oncology
San Antonio, Texas, 78229, United States
Texas Oncology
The Woodlands, Texas, 77380, United States
Texas Oncology
Tyler, Texas, 75702, United States
Intermountain Medical Center
Murray, Utah, 84107, United States
University of Virginia Health System
Charlottesville, Virginia, 22908, United States
Virginia Cancer Specialists, PC
Gainesville, Virginia, 20155, United States
Prince of Wales Hospital
Randwick, New South Wales, 2031, Australia
Icon Cancer Centre Wesley
Auchenflower, Queensland, 4066, Australia
Cancer Research South Australia
Adelaide, South Australia, 5000, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000, Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009, Australia
UZA
Edegem, 2650, Belgium
University Hospital Ghent
Ghent, 9000, Belgium
Princess Margaret Cancer Center
Toronto, Ontario, M5G 1X6, Canada
Centre Hospitalier de l'Universite de Montreal (CHUM)
Montreal, Quebec, H2X 0C1, Canada
McGill University Health Centre
Montreal, Quebec, H4A 3J1, Canada
British of Columbia
Vancouver, V5Z 4E6, Canada
Aalborg U.H
Aalborg, 9000, Denmark
Centre Hospitalier de Besançon
Besançon, 25000, France
Site Georges François Leclerc
Dijon, 21079, France
Centre Oscar Lambret
Lille, 59020, France
Centre Léon Bérard
Lyon, 69373, France
Institut Curie
Paris, France
Agaplesion Markus Krankenhaus
Frankfurt am Main, Hesse, 60431, Germany
Charité - Universitätsmedizin Berlin
Berlin, 13353, Germany
Universitätsklinikum Carl Gustav Carus
Dresden, 01307, Germany
Kliniken Essen-Mitte
Essen, 45136, Germany
UMC Hamburg-Eppendorf
Hamburg, 20246, Germany
Universitätsklinikum Mannheim GmbH
Mannheim, 68167, Germany
Universitätsfrauenkinik Ulm
Ulm, 89075, Germany
St. James's Hospital
Dublin, 08, Ireland
Centro di Riferimento Oncologico (CRO)
Aviano, 33081, Italy
Spedali Civili
Brescia, 25123, Italy
AO Cannizzaro
Catania, 95126, Italy
San Raffaele Hospital
Milan, 20132, Italy
Humanitas San Pio X
Milan, 20159, Italy
European Institute of Oncology (IEO)
Milan, Italy
Istituto Nazionale dei Tumori
Milan, 20133, Italy
INT Napoli Hospital
Naples, Italy
Istituto Oncologico Veneto (IOV)
Padova, 35128, Italy
IRCCS Gemelli
Roma, 00168, Italy
Istituti Fisioterapici Ospitalieri
Rome, 00144, Italy
S.C.D.U. Oncologia
Torino, 10128, Italy
The Mie University Hospital
Tsu, Mie-ken, 514-8507, Japan
Aichi Cancer Center Hospital
Aichi, Nagoya, 464-8681, Japan
Tohoku University Hospital
Miyagi, 980-8574, Japan
Osaka Medical Center
Osaka, Japan
The Jikei University Hospital
Tokyo, 3-19-18, Japan
Netherlands Cancer Insitute
Amsterdam, 1066, Netherlands
Radboud UMC
Nijmegen, 6525 GA, Netherlands
Auckland City Hospital
Auckland, 1023, New Zealand
Białostockie Centrum Onkologii
Bialystok, 15-027, Poland
Gdański Uniwersytet Medyczny
Gdansk, 80-214, Poland
Siedleckie Centrum Onkologii
Siedlce, 98-110, Poland
Seoul National University Bundang Hospital
Seongnam, 13620, South Korea
Yonsei University Severance Hospital
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Gangnam Severance Hospital
Seoul, 06273, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Clínico Virgen de La Arrixaca
El Palmar, Murcia, 30120, Spain
H. de Donostia
Donostia / San Sebastian, San Sebastian, 20014, Spain
H. Vall d´ Hebron
Barcelona, Spain
Hospital Universitario Reina Sofía
Córdoba, Spain
H.U. Ramón y Cajal
Madrid, Spain
Hospital Clínico Universitario de Santiago
Santiago de Compostela, 15706, Spain
Hospital Clínico Universitario de Valencia
Valencia, 46010, Spain
Greater Glasgow and Clyde (GGC)
Glasgow, Scotland, G120YN, United Kingdom
Cambridge University Hospital
Cambridge, CB2 0QQ, United Kingdom
University of Edinburgh Cancer Research Centre
Edinburgh, United Kingdom
Hope Cancer Trials Centre
Leicester, LE2 7LX, United Kingdom
University College London Hospitals NHS Foundation Trust
London, NW1 2PG, United Kingdom
Royal Marsden Hospital
London, SW7 3RP, United Kingdom
The Christie NHS Foundation Trust
Manchester, United Kingdom
Royal Marsden Hospital
Sutton, SM2 5PT, United Kingdom
Related Publications (3)
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. The combination of avutometinib and defactinib in treating recurrent low-grade serous ovarian cancer: a plain language summary of the Phase II clinical trial ENGOT-OV60/GOG-3052/RAMP 201. Future Oncol. 2025 Dec;21(30):3859-3871. doi: 10.1080/14796694.2025.2595130. Epub 2025 Dec 12.
PMID: 41384753DERIVEDBanerjee 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: 40644648DERIVEDGrisham R, Monk BJ, Van Nieuwenhuysen E, Moore KN, Fabbro M, O'Malley DM, Oaknin A, Thaker P, Oza AM, Colombo N, Gershenson D, Aghajanian CA, Choi CH, Lee YC, Mirza MR, Coleman RL, Cobb L, Harter P, Lustgarten S, Youssoufian H, Banerjee S. GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301: a phase 3, randomized trial evaluating avutometinib plus defactinib compared with investigator's choice of treatment in patients with recurrent low grade serous ovarian cancer. Int J Gynecol Cancer. 2025 Nov;35(11):101832. doi: 10.1136/ijgc-2024-005919. Epub 2025 Apr 19.
PMID: 39375168DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rachel Grisham, MD
GOG Foundation
- PRINCIPAL INVESTIGATOR
Susana Banerjee, MBBS, MA, PhD
European Network of Gynaecological Oncological Trial Groups (ENGOT)
- STUDY DIRECTOR
Craig Berman Verastem Medical Monitor
RAMP301@verastem.com
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 2, 2023
First Posted
October 10, 2023
Study Start
March 18, 2024
Primary Completion (Estimated)
October 15, 2028
Study Completion (Estimated)
February 9, 2031
Last Updated
July 31, 2026
Record last verified: 2026-07