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A Phase 2 Study of Avutometinib (VS-6766) Plus Defactinib | Clinical Trials | Clareo Health

RECRUITINGPHASE2

A Phase 2 Study of Avutometinib (VS-6766) Plus Defactinib

A Phase 2 Study of VS-6766 (Dual RAF/MEK Inhibitor) Plus Defactinib (FAK Inhibitor) in Recurrent Gynecological Cancers (DURAFAK)

NCT05512208•University of Oklahoma

View on ClinicalTrials.gov

Summary

The purpose of this research is to test the effectiveness and safety of the study drugs (VS-6766 and defactinib), and see what effects (good and bad) these drugs have on the patients with endometrioid cancer, mucinous ovarian cancer, high-grade serous ovarian cancer, or solid gynecological cancer.

Detailed Description

This is a single-stage exploratory, Phase 2, multicenter, parallel cohort, open label study designed to evaluate efficacy and safety of VS-6766 + defactinib. Enrolled study patients will receive the study drugs (VS-6766 and defactinib) to take orally based on the study procedures. Patients will follow the study procedures and attend all the study visits where various procedures including physical examinations, vitals, assessing the size of the patient's tumor, and examination of urine and blood may take place. Additional visits may be done to assess any other side effects a patient's experiences.

Eligibility

Age

18 - 99 years

Sex

FEMALE

Healthy Volunteers

Inclusion Criteria

•1. Female subjects ≥ 18 years of age.
•2. Histologically proven gynecological cancers (endometrioid, MOC, HGSOC and solid gynecological cancers) with mutated RAS, BRAF (type I, II, and/or III), NF-1 loss of function, and/or RAS activation.
•1. Mutational status will be taken from the previous next-gen sequencing (NGS) or molecular testing results and reviewed by the Principal Investigator prior to the start of treatment.
•2. Adequate pathology material (as defined in the lab manual) must be available prior to treatment assignment to be used for confirmation.
•3. Tumor with known RAS mutation, BRAF (type I, II, and/or III) mutation, NF-1 and/or RAS activation status determined from previous NGS or molecular testing. Adequate archival tumor tissue less than 5 years old or fresh biopsy tissue samples (as defined in the lab manual) must be available.
•4. Progression (radiographic or clinical) or recurrence of gynecological cancer after at least one prior systemic therapy for metastatic disease. Below are additional prior treatments that are allowed once the requirement of prior platinum therapy is satisfied.
•a. Prior systemic therapy for metastatic disease (FIGO stage II-IV) may consist of chemotherapy administered as single agent or a platinum or another chemotherapy doublet with or without bevacizumab, with or without maintenance therapy or radiation therapy; and/or hormonal therapy.
•5. Measurable disease according to RECIST 1.1.
•6. An Eastern Cooperative Group (ECOG) performance status ≤ 2.
•7. Must have adequate organ function defined by the following laboratory parameters:
+24 more criteria

Exclusion Criteria

•1. Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy.
•2. Prior MEKi or RAFi exposure.
•3. Low grade serous ovarian cancer (LGSOC).
•4. History of prior malignancy with recurrence \<3 years from the time of enrollment. Subjects with basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, and in situ cervical cancer that has undergone potentially curative therapy with no evidence of disease recurrence for ≥1 year since completion of the appropriate therapy may be included. Subjects with other malignancies associated with very low risk of metastasis or death may be included upon discussion with the PI.
•5. Subjects who are deemed in the opinion of their treating physician to be appropriate candidates for a debulking surgery. These subjects should preferentially receive surgery prior to consideration of trial therapy.
•6. Major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks, or palliative radiotherapy within 1 week (7 days) of the first dose of study therapy.
•7. Treatment with warfarin. Subjects on warfarin for DVT/PE can be converted to low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs).
•8. Exposure to strong CYP2C9 and CYP3A4 inhibitors or inducers within 14 days prior to the first dose and during the course of therapy. See Table 14 and Table 15 for representative lists of CYP inhibitors and inducers. For additional guidance, see https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteractions-table-substrates-inhibitors-and-inducers.
•9. Exposure to P-glycoprotein (P-gp) inhibitors or inducers within 14 days prior to the first dose and during the course of the study. See Table 16 for a representative list of P-gp inhibitors and inducers.

Locations (4)

AdventHealth

Orlando, Florida, United States

Louisiana State University Medical Center New Orleans

New Orleans, Louisiana, United States

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, United States

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Key Dates

Start Date

February 6, 2023

Primary Completion Date

December 1, 2027

Completion Date

December 1, 2029

Last Updated

October 22, 2025

Enrollment

ESTIMATED participants

Conditions

Endometrioid CancerMucinous Ovarian CancerHigh Grade Serous Ovarian CancerCervical CancerSolid Tumor

Interventions

Avutometinib (VS-6766) + defactinib

DRUG

Contacts

SCC IIT Office

CONTACT

4052718777 SCC-IIT-Office@ouhsc.edu

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: October 22, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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A Phase 2 Study of Avutometinib (VS-6766) Plus Defactinib

Inclusion Criteria

Exclusion Criteria

Unravelling Tumour Biology In Ovarian Cancer With Precision Imaging

Role of RPL8 Protein Alterations in High-grade Serous Ovarian Carcinoma

A Study of KB-0742 in Participants With Relapsed or Refractory Solid Tumors Including Platinum Resistant High Grade Serous Ovarian Cancer (HGSOC)

Using Genetic Profile to Determine the Treatment for Patients With Ovarian Cancer Who Previously Received a PARP-inhibitor

Bevacizumab Plus Modiifed FOLFIRINOX in Ovarian, Fallopian Tube, or Primary Peritoneal Mucinous Carcinoma

Expanded Access to Veliparib