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

NCT06682572 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: VS-6766-201JjRCT2021240021
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 5

Brief Summary

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)

Conditions

Low Grade Serous Ovarian Cancer; Ovarian Cancer

Keywords

KRAS; KRAS wt; KRAS mt

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Duration of Response

  12 months

• Objective response rate (ORR)

  12 months

• Progression free survival (PFS)

  24 months

• Disease control rate (DCR)

  6 months

• Clinical benefit rate

  6 months

Study Arms (1)

avutometinib + defactinib

EXPERIMENTAL

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)

Interventions

Avutometinib (VS-6766) + Defactinib (VS-6063) DRUG

combination therapy

avutometinib + defactinib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Verastem, Inc.: lead
• Japanese Gynecologic Oncology Group: collaborator

Study Sites (5)

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, 464-8681, Japan

Location

Kurume University Hospital

Kurume, Fukuoka, 830-0011, Japan

Location

Mie University Hospital

Tsu, Mie-ken, 514-8507, Japan

Location

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

Location

Jikei University Hospital

Minato, Tokyo, 105-0003, Japan

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

defactinib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2024
• First Posted: November 12, 2024
• Study Start: October 30, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): October 1, 2027
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

JP (5)