Mesonephric Gynecologic CancerPhase 2NCT05787561

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

A Phase 2 study testing Avutometinib (VS-6766) and Defactinib in people with Mesonephric Gynecologic Cancer, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

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

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Mesonephric Gynecologic Cancer
What is being tested?: Avutometinib (VS-6766) and Defactinib
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 40 participants
Where: 7 sitesUnited States
Study dates: 15 Mar 2023to Mar 2027
Phase: Phase 2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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
vasectomized partner
sexual abstinence
Patients must have adequate cardiac function with left ventricular ejection fraction ≥ 55% by echocardiography (ECHO)
Baseline QTc interval < 460 ms (average of triplicate readings) (Common Terminology Criteria for Adverse Events [CTCAE] Grade 1) using Fredericia's QT correction formula. NOTE: This criterion does not apply to patients with a right or left bundle branch block.
Must have adequate organ function defined by the following laboratory parameters:
Total Bilirubin: ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x ULN may be enrolled)
AST(SGOT)/ALT(SGPT): ≤3 × institutional ULN
Adequate renal function defined as either:
Creatinine clearance (CrCL) or estimated Glomerular filtration rate (eGFR) of ≥50 mL/min estimated using either the Cockcroft-Gault equation, the Modification of Diet in Renal Disease Study, or as reported in the comprehensive metabolic panel/basic metabolic panel (eGFR).
Or:
Serum Creatinine ≤ 1.5 x ULN
Creatine phosphokinase (CPK) ≤ 2.5 x ULN.
Adequate hematologic function including: hemoglobin [Hb] ≥ 9.0 g/dL; platelets ≥ 100,000/mm^3; and absolute neutrophil count [ANC] ≥ 1000/mm^3

Who cannot join

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

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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.
strong breast cancer resistance protein (BCRP) inhibitors or inducers, due to potential drug-drug interactions with avutometinib and defactinib.

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

United States7 sites

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920
Memorial Sloan Kettering Suffolk -Commack (Limited Protocol Activities)
Commack, New York, 11725
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, 10604
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, 07748
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Uniondale, New York, 11553

Other trials in United States

About this study

Official title: Single Arm Phase II Study of Avutometinib (VS-6766) and Defactinib in Advanced or Recurrent Mesonephric Gynecologic Cancer

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
Being tested: Avutometinib (VS-6766), Defactinib
Keywords: Avutometinib (VS-6766), Defactinib, 22-392

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Avutometinib (VS-6766)Drug
3.2 mg PO, twice weekly
DefactinibDrug
200 mg PO BID for 3 weeks, followed by a 1 week rest period, in each 4-week (28 day) cycle.

Study groups in NCT05787561
Study group	Role	What they receive
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. Receives: Drug: Avutometinib (VS-6766); Drug: Defactinib

What is being measured

The primary outcome is the main question the study is designed to answer.

best overall response
as determined by RECIST 1.1
Measured: 2 years

Secondary outcomes (1)

Incidence and severity of adverse events
will be collected at each visit and tabulated with grading by CTCAE Version 5 criteria.
Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Mar 2023Mar 2027

First posted28 Mar 2023
Study start15 Mar 2023
Primary completionMar 2027 (estimated)
Study completionMar 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Mesonephric Gynecologic CancerStudies of the same condition, open and under way.
More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05787561
Sponsor's protocol ID: 22-392
Status last verified: Oct 2026
First submitted: 15 Mar 2023
Last updated: 8 Oct 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Study at a glance

From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Single Arm Phase II Study of Avutometinib (VS-6766) and Defactinib in Advanced or Recurrent Mesonephric Gynecologic Cancer
ClinicalTrials.gov ID: NCT05787561
Acronym / sponsor ID: 22-392
Conditions: Mesonephric Gynecologic Cancer
Keywords: Avutometinib (VS-6766), Defactinib, 22-392
Phase: Phase 2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 40 participants (actual)
Lead sponsor: Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
Collaborators: Verastem, Inc.
Study start: 15 Mar 2023 (actual)
Primary completion: Mar 2027 (estimated)
Study completion: Mar 2027 (estimated)
First posted: 28 Mar 2023 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Avutometinib (VS-6766) and Defactinib	Experimental	Drug: Avutometinib (VS-6766), Drug: DefactinibAll 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.

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (28 listed)

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.

Key exclusion criteria (16 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Avutometinib (VS-6766)3.2 mg PO, twice weekly	Drug	Avutometinib (VS-6766) and Defactinib
Defactinib200 mg PO BID for 3 weeks, followed by a 1 week rest period, in each 4-week (28 day) cycle.	Drug	Avutometinib (VS-6766) and Defactinib

Primary outcome

best overall response
Time frame: 2 years
as determined by RECIST 1.1

1 secondary outcome

Incidence and severity of adverse events
Time frame: 2 years

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2026.
Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Rachel Grisham, MD principal investigator

Memorial Sloan Kettering Cancer Center

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Avutometinib (VS-6766) and Defactinib in people with Mesonephric Gynecologic Cancer, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

best overall response (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05787561.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026.