A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer

Recruitment Status: RECRUITING
(See Contacts and Locations)Verified March 2026 by Verastem, Inc.
Sponsor: Verastem, Inc.
Information Provided by (Responsible Party): Verastem, Inc.

Clinicaltrials.gov Identifier: NCT06072781
Other Study ID Numbers:: VS-6766-301

First Submitted: October 1, 2023
First Posted: October 9, 2023
Last Update Posted: April 1, 2026
Last Verified: March 2026

ClinicalTrials.gov processed this data on March 2026. Link to the current ClinicalTrials.gov record .

Study Details

Study Description

This international, randomized, open-label, Phase 3 study will compare the investigational combination of avutometinib plus defactinib versus Investigator's Choice of Treatments (ICT) in patients with recurrent LGSOC who have progressed on a prior platinum-based therapy. Avutometinib and defactinib are both types of drugs called kinase inhibitors. Kinase inhibitors block cancer cell growth. The study will compare the progression-free survival (PFS) of the combination of avutometinib plus defactinib versus ICT. The study will also evaluate the effect of the combination on safety, overall survival, other efficacy endpoints, and health-related quality of life and disease related symptoms. The study is being conducted by gynecological cancer specialists. Patients who are eligible and agree to participate in this study will be treated with either a combination of avutometinib with defactinib, or with one of four standard of care NCCN and ESMO treatment recommendations for recurrent LGSOC, and then with subsequent follow up appointments. Patients who originally received one of the standards of care treatments who are determined to have progressive disease may be eligible to crossover to receive the investigational combination avutometinib plus defactinib.Avutometinib and defactinib are investigational drugs that have not been approved by the U.S. Food and Drug Administration (FDA)

Condition or Disease	Intervention/Treatment
Low Grade Serous Ovarian Cancer	Drug: avutometinibDrug: Pegylated liposomal doxorubicin

Study Design

Study Type	Interventional
Actual Enrollment	270 participants
Design Allocation	Randomized
Interventional Model	Crossover Assignment
Masking	None (Open Label)
Primary Purpose	Treatment
Official Title	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)
Study Start Date	March 17, 2024
Actual Primary Completion Date	2yrs 4mos from now
Actual Study Completion Date	4yrs 8mos from now

Groups and Cohorts

Group/Cohort	Intervention/Treatment
avutometinib + defactinib Avutometinib 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.	Drug: avutometinib Avutometinib: administered orally
Investigator Choice of Treatment (ICT) Patients 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.	Drug: Pegylated liposomal doxorubicin administered intravenously

Group/Cohort

Intervention/Treatment

avutometinib + defactinib: Avutometinib 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.

Drug: avutometinib: Avutometinib: administered orally

Investigator Choice of Treatment (ICT): Patients 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.

Drug: Pegylated liposomal doxorubicin: administered intravenously

Outcome Measures

Primary Outcome Measures

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)

Secondary Outcome Measures

Overall Survival (OS)
From the time of first dose of study intervention to PD as assessed per RECIST 1.1 or death from any cause
Progression Free Survival (PFS) per investigator assessment
Progression-free survival (PFS) according to RECIST version 1.1, per blinded independent central review (BICR)
Objective response rate (ORR)
From the time of first dose of study intervention to PD as assessed per RECIST 1.1 by Investigator or death from any cause
Duration of Response (DOR)
From the time of first dose of study intervention to PD as assessed per RECIST 1.1 by Investigator or death from any cause
Disease Control Rate (DCR)
CR+PR+Stable disease
Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs)
Count of AE and SAEs by grade, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale
Area under the plasma concentration-time curve (AUC) of avutometinib, defactinib and relative metabolites
Area under plasma Concentration (AUC) 0 to t
Maximum plasma concentration (Cmax) of avutometinib, defactinib and relative metabolites
maximum plasma concentration
To assess the health-related quality of life and disease based on European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire Core module C30 (QLQ-C30).
The EORTC QLQ-C30 is a validated questionnaire to assess the quality of life of ovarian cancer patients.
To assess the health-related quality of life and disease based on European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire Ovarian Cancer module OV28 (QLQ-OV28).
The EORTC QLQ-OV28 is a validated questionnaire to assess the quality of life of ovarian cancer patients.
To assess the health-related quality of life and disease based on EuroQol-5 Dimension 5-level (EQ-5D-5L)
The EuroQol-5 Dimension 5-level (EQ-5D-5L) is a validated questionnaire used to measure a patient's overall health.

Eligibility Criteria

Ages Eligible for Study	(Adult, Older Adult)
Sexes Eligible for Study	Female
Accepts Healthy Volunteers	No
Inclusion Criteria	Patients may be eligible for inclusion in the study if they meet the following criteria: 1. Histologically proven LGSOC (ovarian, fallopian, peritoneal) 2. Documented mutational status of KRAS by a validated tumor-tissue based diagnostic test. 3. Suitable for treatment with at least one of the Investigator's Choice of Treatments:pegylated liposomal doxorubicin, paclitaxel, letrozole, anastrozole. 4. Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease. 5. Measurable disease according to RECIST v1.1. 6. An Eastern Cooperative Group (ECOG) performance status ≤ 1. 7. Adequate organ function. 8. Adequate recovery from toxicities related to prior treatments. 9. For patients with reproductive potential, a negative pregnancy test must be confirmed and agreement to use highly effective method of contraceptive. 10. Willingness to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
Exclusion Criteria	Patients will be excluded from the study if they meet any of the following criteria: 1. Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy. 2. Co-existing high-grade serous ovarian cancer or mixed histology. 3. Prior treatment with avutometinib, defactinib, or other FAK inhibitors. 4. History of prior malignancy with recurrence \<3 years from the time of enrollment. 5. Major surgery within 4 weeks, minor surgery within 1 week, or palliative radiotherapy within 1 week of the first dose of study intervention. 6. Symptomatic brain metastases requiring steroids or other interventions, known leptomeningeal metastases, or spinal cord compression. 7. An active skin disorder that has required systemic therapy within one year of the first dose of study intervention. 8. History of medically significant rhabdomyolysis. 9. For subjects with prior MEK or RAF exposure, Grade 4 toxicity is deemed related to the MEK inhibitor. 10. Symptomatic bowel obstruction within 3 months of the first dose of study intervention 11. Concurrent ocular disorders. 12. Concurrent heart disease or severe obstructive pulmonary disease. 13. Active or past medical history of interstitial lung disease/pneumonitis, including drug-induced or radiation pneumonitis, pulmonary fibrosis, or adult respiratory distress syndrome (ARDS). 14. Subjects with the inability to swallow oral medications. 15. History of hypersensitivity to any of the active agents or ingredients of study intervention: peanut, soya, polyoxyl castor oil, etcetc.). Prior hypersensitivity to anthracyclines or anthracenediones if the use of pegylated liposomal doxorubicin (PLD) is planned. 16. Pregnant or breastfeeding. 17. Active, uncontrolled infection (bacterial, viral, or fungal) requiring systemic therapy.

Contacts and Locations

Sponsors and Collaborators	Verastem, Inc.
Locations	HonorHealth \| Phoenix Arizona, United States, 85016University of Arkansas \| Little Rock Arkansas, United States, 72205UCLA Health \| Los Angeles California, United States, 90095UC Davis \| Sacramento California, United States, 95817University of California, San Francisco \| San Francisco California, United States, 94143Yale University \| New Haven Connecticut, United States, 06520Florida Cancer Specialists - South \| Fort Myers Florida, United States, 33901Mount Sinai \| Miami Beach Florida, United States, 33140AdventHealth \| Orlando Florida, United States, 32804Moffitt Cancer Center \| Tampa Florida, United States, 33612Florida Cancer Specialists Research East \| West Palm Beach Florida, United States, 33401Winship Cancer Institute at Emory University \| Atlanta Georgia, United States, 30322NorthShore University HealthSystem \| Evanston Illinois, United States, 60201Louisiana State University \| New Orleans Louisiana, United States, 70112Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins \| Baltimore Maryland, United States, 21287Karmanos Cancer Center \| Detroit Michigan, United States, 48201Minnesota Oncology Hematology \| Minneapolis Minnesota, United States, 55404Washington University School of Medicine \| St Louis Missouri, United States, 63110Roswell Park Cancer Institute \| Buffalo New York, United States, 14263Memorial Sloan Kettering Cancer Center \| New York New York, United States, 10065Atrium Health \| Charlotte North Carolina, United States, 28203Cleveland Clinic Foundation \| Cleveland Ohio, United States, 44195Ohio State \| Hilliard Ohio, United States, 43026University of Oklahoma Medical Center \| Oklahoma City Oklahoma, United States, 73104Willamette Valley Cancer Institute \| Eugene Oregon, United States, 97401Northwest Cancer Specialists \| Portland Oregon, United States, 97227Asplundh Cancer Pavilion \| Jefferson Health \| Philadelphia Pennsylvania, United States, 19090Allegheny Health Network \| Pittsburgh Pennsylvania, United States, 15224Texas Oncology Central \| Austin Texas, United States, 78731Texas Oncology-Fort Worth Cancer Center \| Fort Worth Texas, United States, 76104Houston Methodist \| Houston Texas, United States, 77030MD Anderson Cancer Center \| Houston Texas, United States, 77030Texas Oncology \| San Antonio Texas, United States, 78229Texas Oncology \| The Woodlands Texas, United States, 77380Texas Oncology \| Tyler Texas, United States, 75702Intermountain Medical Center \| Murray Utah, United States, 84107University of Virginia Health System \| Charlottesville Virginia, United States, 22908Virginia Cancer Specialists, PC \| Gainesville Virginia, United States, 20155Prince of Wales Hospital \| Randwick New South Wales, Australia, 2031Icon Cancer Centre Wesley \| Auchenflower Queensland, Australia, 4066Cancer Research South Australia \| Adelaide South Australia, Australia, 5000Peter MacCallum Cancer Centre \| Melbourne Victoria, Australia, 3000Sir Charles Gairdner Hospital \| Nedlands Western Australia, Australia, 6009UZA \| Edegem , Belgium, 2650University Hospital Ghent \| Ghent , Belgium, 9000Princess Margaret Cancer Center \| Toronto Ontario, Canada, M5G 1X6Centre Hospitalier de l'Universite de Montreal (CHUM) \| Montreal Quebec, Canada, H2X 0C1McGill University Health Centre \| Montreal Quebec, Canada, H4A 3J1British of Columbia \| Vancouver , Canada, V5Z 4E6Aalborg U.H \| Aalborg , Denmark, 9000Centre Hospitalier de Besançon \| Besançon , France, 25000Site Georges François Leclerc \| Dijon , France, 21079Centre Oscar Lambret \| Lille , France, 59020Centre Léon Bérard \| Lyon , France, 69373Institut Curie \| Paris , France, Agaplesion Markus Krankenhaus \| Frankfurt am Main Hesse, Germany, 60431Charité - Universitätsmedizin Berlin \| Berlin , Germany, 13353Universitätsklinikum Carl Gustav Carus \| Dresden , Germany, 01307Kliniken Essen-Mitte \| Essen , Germany, 45136UMC Hamburg-Eppendorf \| Hamburg , Germany, 20246Universitätsklinikum Mannheim GmbH \| Mannheim , Germany, 68167Universitätsfrauenkinik Ulm \| Ulm , Germany, 89075St. James's Hospital \| Dublin , Ireland, 08Centro di Riferimento Oncologico (CRO) \| Aviano , Italy, 33081Spedali Civili \| Brescia , Italy, 25123AO Cannizzaro \| Catania , Italy, 95126San Raffaele Hospital \| Milan , Italy, 20132Humanitas San Pio X \| Milan , Italy, 20159European Institute of Oncology (IEO) \| Milan , Italy, Istituto Nazionale dei Tumori \| Milan , Italy, 20133INT Napoli Hospital \| Naples , Italy, Istituto Oncologico Veneto (IOV) \| Padova , Italy, 35128IRCCS Gemelli \| Roma , Italy, 00168Istituti Fisioterapici Ospitalieri \| Rome , Italy, 00144S.C.D.U. Oncologia \| Torino , Italy, 10128The Mie University Hospital \| Tsu Mie-ken, Japan, 514-8507Aichi Cancer Center Hospital \| Aichi Nagoya, Japan, 464-8681Tohoku University Hospital \| Miyagi , Japan, 980-8574Osaka Medical Center \| Osaka , Japan, The Jikei University Hospital \| Tokyo , Japan, 3-19-18Netherlands Cancer Insitute \| Amsterdam , Netherlands, 1066Radboud UMC \| Nijmegen , Netherlands, 6525 GAAuckland City Hospital \| Auckland , New Zealand, 1023Białostockie Centrum Onkologii \| Bialystok , Poland, 15-027Gdański Uniwersytet Medyczny \| Gdansk , Poland, 80-214Siedleckie Centrum Onkologii \| Siedlce , Poland, 98-110Seoul National University Bundang Hospital \| Seongnam , South Korea, 13620Yonsei University Severance Hospital \| Seoul , South Korea, 03722Asan Medical Center \| Seoul , South Korea, 05505Gangnam Severance Hospital \| Seoul , South Korea, 06273Samsung Medical Center \| Seoul , South Korea, 06351Clínico Virgen de La Arrixaca \| El Palmar Murcia, Spain, 30120H. de Donostia \| Donostia / San Sebastian San Sebastian, Spain, 20014H. 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 , Spain, 15706Hospital Clínico Universitario de Valencia \| Valencia , Spain, 46010Greater Glasgow and Clyde (GGC) \| Glasgow Scotland, United Kingdom, G120YNCambridge University Hospital \| Cambridge , United Kingdom, CB2 0QQUniversity of Edinburgh Cancer Research Centre \| Edinburgh , United Kingdom, Hope Cancer Trials Centre \| Leicester , United Kingdom, LE2 7LXUniversity College London Hospitals NHS Foundation Trust \| London , United Kingdom, NW1 2PGRoyal Marsden Hospital \| London , United Kingdom, SW7 3RPThe Christie NHS Foundation Trust \| Manchester , United Kingdom, Royal Marsden Hospital \| Sutton , United Kingdom, SM2 5PT
Investigators	Principal Investigator: Rachel Grisham, MD, GOG FoundationPrincipal Investigator: Susana Banerjee, MBBS, MA, PhD, European Network of Gynaecological Oncological Trial Groups (ENGOT)Study Director: Craig Berman Verastem Medical Monitor, RAMP301@verastem.com

More Information

Publications

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. 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. Grisham 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.