A Study of Avutometinib + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer in Japanese Patients (RAMP201J)

December 15, 2025 updated by: Verastem, Inc.

A Phase 2 Study of Avutometinib (VS-6766, a Dual RAF/MEK Inhibitor) In Combination With Defactinib (FAK Inhibitor) in Recurrent Low-Grade Serous Ovarian Cancer (LGSOC) in Japanese Patients

This study will confirm the safety and efficacy of avutometinib in combination with defactinib in Japanese patients with recurrent Low-Grade Serous Ovarian Cancer (LGSOC)

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a multi-center, open label Phase 2 study designed to evaluate safety and tolerability and confirm efficacy by BICR of avutometinib in combination with defactinib in Japanese patients with molecularly profiled recurrent LGSOC.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
    • Aichi-ken
      • Nagoya, Aichi-ken, Japan, 464-8681
        • Aichi Cancer Center Hospital
    • Fukuoka
      • Kurume, Fukuoka, Japan, 830-0011
        • Kurume University Hospital
    • Mie-ken
      • Tsu, Mie-ken, Japan, 514-8507
        • Mie University Hospital
    • Miyagi
      • Sendai, Miyagi, Japan, 980-8574
        • Tohoku University Hospital
    • Tokyo
      • Minato, Tokyo, Japan, 105-0003
        • Jikei University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically proven LGSOC (ovarian, peritoneal)
  • Documented mutational status of KRAS by validated diagnostic test of tumor tissue
  • Documented disease progression (radiographic or clinical) or recurrence of LGSOC and have received at least one platinum-based chemotherapy agent
  • 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, excluding ovarian cancer, 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
  • Patients with the inability to swallow oral medications

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: avutometinib + defactinib
Avutometinib 3.2mg, 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 (VS-6766) + Defactinib (VS-6063)
combination therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Confirmed overall response rate (ORR; partial response [PR] + complete response [CR]
Time Frame: From start of treatment to confirmation of response; 24 weeks
Confirmed overall response rate (ORR; partial response [PR] + complete response [CR] defined according to Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1]) as assessed by the blinded independent central radiology review committee (BICR)
From start of treatment to confirmation of response; 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response
Time Frame: 12 months
From the time of first dose of study intervention to PD as assessed by RECIST 1.1 or death from any cause
12 months
Objective response rate (ORR)
Time Frame: 12 months
From the time of first dose of study intervention to PD as assessed by RECIST 1.1 by Investigator or death from any cause.
12 months
Progression free survival (PFS)
Time Frame: 24 months
From the time of first dose of study intervention to first documentation of progressive disease (PD) or death by any cause
24 months
Disease control rate (DCR)
Time Frame: 6 months
CR + PR + SD
6 months
Clinical benefit rate
Time Frame: 6 months
CR + PR + (SD >6 months)
6 months
Overall Survival (OS)
Time Frame: up to 2 years
From the time of first dose of study intervention to PD as assessed by RECIST 1.1 or death from any cause
up to 2 years
Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: 18 months
Count of AE and SAEs by grade, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale
18 months
Area under the plasma concentration-time curve (AUC) of avutometinib, defactinib and relative metabolites
Time Frame: 9 months
Area under Plasma Concentration (AUC) 0 to t
9 months
Maximum plasma concentration (Cmax) of avutometinib, defactinib and relative metabolites
Time Frame: 9 months
Maximum Plasma Concentration
9 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Verastem, Inc.

Collaborators

Japanese Gynecologic Oncology Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 30, 2024

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

October 1, 2027

Study Registration Dates

First Submitted

November 5, 2024

First Submitted That Met QC Criteria

November 7, 2024

First Posted (Actual)

November 12, 2024

Study Record Updates

Last Update Posted (Actual)

December 17, 2025

Last Update Submitted That Met QC Criteria

December 15, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VS-6766-201J
  • jRCT2021240021 (Other Identifier: Japan Registry of Clinical Trials)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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