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Low Grade Ovarian Serous AdenocarcinomaPhase 2RAMP 201NCT04625270

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

A Phase 2 study testing avutometinib (VS-6766) and avutometinib (VS-6766) and defactinib in people with Low Grade Ovarian Serous Adenocarcinoma and Ovarian Cancer, run by Verastem, Inc. at 47 sites in 7 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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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) Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
avutometinib (VS-6766) and avutometinib (VS-6766) and defactinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
225 participants
Where
47 sitesin 7 countries
Study dates
21 Dec 2020to Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

47 sites in 7 countries.

47 sites in 7 countries

United States27 sites

  • University of New Mexico Comprehensive Cancer Center

    Albuquerque, New Mexico, 87131

  • Texas Oncology Austin Central

    Austin, Texas, 78731

  • University of Virginia Health System

    Charlottesville, Virginia, 22908

  • University of Chicago

    Chicago, Illinois, 60637

  • Cleveland Clinic Women's Health Institute

    Cleveland, Ohio, 44195

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43212

  • Texas Oncology- Dallas Presbyterian Hospital

    Dallas, Texas, 75231

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • Willamette Valley Cancer Institute and Research Center

    Eugene, Oregon, 97401

  • Virginia Cancer Specialists, PC

    Gainesville, Virginia, 20155

  • Maryland Oncology and Hematology, P.A.

    Glenn Dale, Maryland, 20769

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89128

  • Texas Oncology

    Longview, Texas, 75601

  • Texas Oncology

    McAllen, Texas, 78503

  • Minnesota Oncology Hematology PA

    Minneapolis, Minnesota, 55404

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Yale School of Medicine

    New Haven, Connecticut, 06510

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Oklahoma Medical Center

    Oklahoma City, Oklahoma, 73104

  • Advent Health

    Orlando, Florida, 32804

  • Northwest Cancer Specialists

    Portland, Oregon, 97227

  • Texas Oncology

    San Antonio, Texas, 78240

  • Sansum Clinic

    Santa Barbara, California, 93105

  • Arizona Oncology Associates PC HAL

    Scottsdale, Arizona, 85258

  • Washington University School of Medicine

    St Louis, Missouri, 63110

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

    Tampa, Florida, 33612

  • Texas Oncology

    The Woodlands, Texas, 77380

Other trials in United States

United Kingdom5 sites

  • Western General Hospital

    Edinburgh, EH4 2XU

  • Beatson West of Scotland Cancer Centre

    Glasgow, G120YN

  • UCLH Cancer Clinical Trials Unit

    London, NW1 2PG

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

  • Royal Marsden Hospital

    Sutton

Other trials in United Kingdom

France4 sites

  • Hopital Jean Minjoz

    Besançon, 2500

  • Centre Leon Berard

    Lyon, 69008

  • ICM - Val d'Aurelle

    Montpellier, 34298

  • Institut Curie

    Paris, 75248

Other trials in France

Spain4 sites

  • Hospital Universitario Vall D'Hebron

    Barcelona, 08035

  • Hospital Universitario Reina Sofia

    Córdoba, 14004

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • Hospital Clínico Universitario de Valencia

    Valencia, 46010

Other trials in Spain

Belgium3 sites

  • UZ Gent Medische Oncologie

    Ghent, 9000

  • UZ Leuven

    Leuven, 3000

  • CHU de Liege

    Liège, 4000

Other trials in Belgium

Canada2 sites

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

    Montreal, H2X 0A9

  • Princess Margaret Cancer Centre

    Toronto, M5G2M9

Other trials in Canada

Italy2 sites

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

    Milan, 20141

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

    Padova, 35128

Other trials in Italy

About this study

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)

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)

Read the detailed 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.

Being tested
avutometinib (VS-6766), avutometinib (VS-6766) and defactinib
Keywords
Low Grade Serous Ovarian Cancer, KRAS, KRAS wt
Medical subject headings
Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • avutometinib (VS-6766)Drug

    avutometinib (VS-6766) monotherapy

  • avutometinib (VS-6766) and defactinibDrug

    Also called avutometinib (VS-6766) and VS-6063

    avutometinib (VS-6766) and defactinib combination

Study groups in NCT04625270
Study groupRoleWhat they receive
Part AExperimentalTo 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)
Receives: Drug: avutometinib (VS-6766); Drug: avutometinib (VS-6766) and defactinib
Part BExperimentalTo determine the efficacy of the optimal regimen identified from Part A
Receives: Drug: avutometinib (VS-6766); Drug: avutometinib (VS-6766) and defactinib
Part C:ExperimentalTo evaluate additional efficacy parameters for the optimal regimen identified in Part A.
Receives: Drug: avutometinib (VS-6766) and defactinib
Part DExperimentalTo evaluate additional efficacy parameters for a lower dose of avutometinib in combination with defactinib
Receives: Drug: avutometinib (VS-6766) and defactinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Confirmed overall response rate per RECIST 1.1

    Measured: From start of treatment to confirmation of response; 24 weeks

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

    Confirmed overall response rate per RECIST 1.1

    Measured: From start of treatment to confirmation of response; 24 weeks

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

    Confirmed overall response rate per RECIST 1.1

    Measured: From start of treatment to confirmation of response; 24 weeks

  4. 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

    Measured: From start of treatment to confirmation of response; 24 weeks

Secondary outcomes (5)

  1. Overall Response Rate as assessed by Investigator

    Proportioned subjects achieving a CR or PR as assess by the investigator

    Measured: From start of treatment to confirmation of response; 24 weeks

  2. Duration of Response (DOR)

    From time of first response to PD as assessed by the BIRC

    Measured: 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

  3. Disease Control Rate (DCR)

    CR+PR+stable disease

    Measured: Greater than or equal to 8 weeks

  4. Progression Free Survival (PFS)

    From time of first dose of study intervention to PD or death for any cause

    Measured: Up to 5 years

  5. Overall Survival (OS)

    From time of first dose of study intervention to death

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Nov 2020
  2. Study start21 Dec 2020
  3. Primary completion15 Nov 2024
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
225 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04625270
Sponsor's protocol ID
VS-6766-201
Other IDs
GOG-3052, ENGOT-ov60
Acronym
RAMP 201
Status last verified
Mar 2024
First submitted
5 Nov 2020
Last updated
29 Jan 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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. 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.

    PubMed 40644648

  • 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.

    PubMed 38493021

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing avutometinib (VS-6766) and avutometinib (VS-6766) and defactinib in people with Low Grade Ovarian Serous Adenocarcinoma and Ovarian Cancer, run by Verastem, Inc. at 47 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 29 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 47 sites in United States, United Kingdom, France, Spain, Belgium and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Determine optimal regimen of avutometinib (VS-6766) monotherapy or in combination with defactinib (time frame: From start of treatment to confirmation of response; 24 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04625270, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2025.

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