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

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: Ovarian Cancer; Low Grade Serous Ovarian Cancer
• Intervention / Treatment: Drug: Avutometinib (VS-6766) + Defactinib (VS-6063)

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

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

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

How is the study designed?

Design Details

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

Number of Arms

1

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]	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	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)	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)	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)	CR + PR + SD	6 months
Clinical benefit rate	CR + PR + (SD >6 months)	6 months
Overall Survival (OS)	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)	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	Area under Plasma Concentration (AUC) 0 to t	9 months
Maximum plasma concentration (Cmax) of avutometinib, defactinib and relative metabolites	Maximum Plasma Concentration	9 months

Collaborators and Investigators

• Sponsor: Verastem, Inc.
• Collaborators: Japanese Gynecologic Oncology Group

Publications and helpful links

Helpful Links

• clinical trial listing on Japan Registry of Clinical Trials

Study record dates

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: KRAS; KRAS wt; KRAS mt
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Ovarian Neoplasms; defactinib
• 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