A Study of Avutometinib (VS-6766) and Defactinib in People With Mesonephric Gynecologic Cancer

NCT05787561 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 22-392
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 7

Brief Summary

This study will test if Avutometinib (VS-6766) in combination with Defactinib is an effective treatment for advanced or recurrent mesonephric gynecologic cancer.

Conditions

Mesonephric Gynecologic Cancer

Keywords

Avutometinib (VS-6766); Defactinib; 22-392

Outcome Measures

Primary Outcomes (1)

• best overall response

  as determined by RECIST 1.1

  2 years

Secondary Outcomes (1)

• Incidence and severity of adverse events

  2 years

Study Arms (1)

Avutometinib (VS-6766) and Defactinib

EXPERIMENTAL

All enrolled patients will be treated with Avutometinib (VS-6766) 3.2 mg PO, twice weekly (e.g. M/Th,Tu/F, or W/Sa) + defactinib 200 mg PO BID for 3 weeks, followed by a 1 week rest period, in each 4-week (28 day) cycle.

Drug: Avutometinib (VS-6766); Drug: Defactinib

Interventions

Avutometinib (VS-6766) DRUG

3.2 mg PO, twice weekly

Avutometinib (VS-6766) and Defactinib

Defactinib DRUG

200 mg PO BID for 3 weeks, followed by a 1 week rest period, in each 4-week (28 day) cycle.

Avutometinib (VS-6766) and Defactinib

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Mesonephric Gynecologic Cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients ≥ 18 years of age
• Histologic confirmation of Gynecologic Mesonephric or Mesonephric-like cancer (GMC). Patients with mixed histology are eligible if the disease is deemed by the treating physician to be driven by the GMC component.
• Measurable disease according to RECIST 1.1
• Patients must have persistent (disease that is metastatic at presentation or remains present following first-line therapy) or recurrent disease (disease that has come back or progressed following prior surgery or treatment)
• Patients with metastatic or recurrent disease do not require any prior systemic therapy prior to enrollment. Patients may have received unlimited lines of prior systemic therapy.
• Patients with treated brain metastases are eligible if follow-up brain imaging after CNS-directed therapy shows no evidence of progression. Patients with asymptomatic brain metastases that do not require intervention are also eligible.
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Resolution of all toxicities of prior therapy or surgical procedures to baseline or Grade 1 (except for hypothyroidism requiring medication, and alopecia, which must have resolved to Grade ≤2).
• Female patients with reproductive potential agree to use highly effective method of contraceptive during the trial and for 1 month following the last dose of study intervention. Hormonal forms of contraception are not recommended in this study.
• Non-hormonal methods of highly effective contraception include:
• intrauterine device (IUD)
• bilateral tubal occlusion

You may not qualify if:

• Patients with newly diagnosed localized disease should be treated as per standard of care and are not eligible for this study. Patients who are candidates for potentially curative surgery or radiation are not eligible for this trial.
• Systemic anti-cancer therapy (other than endocrine therapy) within 4 weeks, 1 cycle, or 5 half-lives (whichever is shortest) of the first dose of study intervention; Endocrine therapy within 1 week of the first dose of study intervention.
• Major surgery within 4 weeks , minor surgery within 2 weeks, or palliative radiotherapy within 1 week of the first dose of study intervention.
• Treatment with warfarin. Patients on warfarin for deep vein thrombosis/pulmonary embolism can be converted to low-molecular-weight heparin or direct oral anticoagulants (DOACs).
• Prior treatment with a MEK or RAF or FAK inhibitor
• Patients with the inability to swallow oral medications or impaired gastrointestinal absorption due to gastrectomy or drainage PEG tube
• Patients with history of retinal pathology or evidence of visible retinal pathology that is considered a risk factor for RVO, intraocular pressure \> 21 mm Hg as measured by tonometry, or other significant ocular pathology, such as anatomical abnormalities that increase the risk for RVO
• Patients with a history of corneal erosion (instability of corneal epithelium), corneal degeneration, active or recurrent keratitis, and other forms of serious ocular surface inflammatory conditions.
• History of rhabdomyolysis
• Patients with a history of hypersensitivity to any of the active or inactive avutometinib (VS-6766) and defactinib ingredients (hydroxypropylmethylcellulose, mannitol, magnesium stearate) of the investigational product.
• Any other medical condition (e.g., cardiac, gastrointestinal, pulmonary, psychiatric, neurological, genetic, etc.) that in the opinion of the Investigator would places the patient at unacceptably high risk for toxicity.
• Exposure to medications (with or without prescriptions), supplements, herbal remedies, or foods with potential for drug-drug interactions with study interventions within 14 days prior to the first dose of study intervention and during the course of therapy, including:
• strong CYP3A4 inhibitors or inducers, due to potential drug-drug interactions with both avutometinib (VS-6766) and defactinib.
• strong CYP2C9 inhibitors or inducers, due to potential drug-drug interactions with defactinib.
• P-glycoprotein (P-gp) inhibitors or inducers, due to potential drug-drug interactions with defactinib.

Sponsors & Collaborators

• Verastem, Inc.: collaborator
• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk -Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

defactinib

Study Officials

• Rachel Grisham, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel Grisham, MD

CONTACT

646-888-4653; grishamr@mskcc.org

Carol Aghajanian, MD

CONTACT

646-888-4217

Study Design

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

Study Record Dates

• First Submitted: March 15, 2023
• First Posted: March 28, 2023
• Study Start: March 15, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (7)