Phase Ib Study of Avutometinib, Defactinib, and Everolimus in RAS Pathway Mutant Endometrial Cancer

Recruiting now · Phase 1

Conditions studied: Phase IB, Avutometinib, RAS Pathway, Endometrial

In brief

To find the recommended dose of the combination of avutometinib, defactinib, and everolimus in patients with endometrial cancer that is recurrent and has abnormal RAS activity. The safety and effects of this combination will also be studied.

Key facts

Study ID

NCT07318324

Run by

M.D. Anderson Cancer Center

People needed

31

Starts

2026-05-13

Expected to finish

2030-08-01

Last updated by the study team

2026-06-29

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may not qualify if…

• Participants who are pregnant or lactating.
• Participants with sarcoma components of their endometrial cancer, except carcinosarcoma.
• Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤2 weeks prior to cycle 1 day 1.
• Participation in an interventional anti-cancer study (clinical trial) within 3 weeks prior to cycle 1 day 1
• Major surgery within four weeks before cycle 1 day 1.
• A history of congestive heart failure (CHF) of NYHA Class ≥3, or history of myocardial infarction (MI) within 3 months.
• Participants with a history of severe obstructive pulmonary disease, pulmonary hypertension, and/or pulmonary fibrosis in the opinion of treating MD
• History of medically significant rhabdomyolysis in the opinion of treating MD.
• For participants with prior MEK inhibitors, any history of or ongoing Grade 4 toxicity deemed related to MEK inhibitor
• Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; participants with controlled infection in the opinion of treating MD or on prophylactic antibiotics are permitted in the study.
• Activr Hepatitis B, or C infection as indicated by detectable viral load. Known HIV seropositivity with detectable viral load. Participants with an undetectable viral load are eligible for the trial.
• Any underlying condition that would significantly interfere with the absorption of an oral medication or inability to take oral medications in the opinion of treating MD
• Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• Participants with symptomatic brain lesions
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). Subjects with known deep vein thrombosis/pulmonary embolism that are under appropriate anti-coagulation treatment are eligible
• History of clinically significant hemoptysis within 1 month prior to study enrollment for any tumor type.
• Current, non-healing wound, ulcer or bone fractures
• Known hypersensitivity to defactinib, avutometinib, everolimus, and/or other rapamycin derivatives.
• Current warfarin use. Participants who are being treated with warfarin within 7-14 days prior to enrollment for deep vein thrombosis/pulmonary embolism may be eligible if their warfarin therapy can be converted to low molecular weight heparin or direct oral anticoagulants (DOACs). Participants who can be transitioned should have INR checked after 5 days on low molecular weight heparin or a direct oral anticoagulant (DOAC).
• Participants are eligible if the INR is ≤ 1.5 prior to the first study dose.
• Current use of medications (with or without prescriptions), supplements, herbal remedies, or foods (Grapefruit and grapefruit juice, Seville oranges and star fruit) with potential for drug-drug interactions with avutometinib and/or defactinib within 5 half-lives (if known), or if not known then 14 days prior to the first dose of study intervention, including:
• Strong CYP3A4 inhibitors or inducers
• Strong CYP2C9 inhibitors or inducers
• Strong P-glycoprotein (P-gp) inhibitors or inducers
• Strong breast cancer resistance protein (BCRP) inhibitors or inducers

Where it is running

• MD Anderson Cancer Center — Houston, Texas, United States (enrolling)

Full record on ClinicalTrials.gov

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