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

NCT07318324 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2025-1174NCI-2025-09476
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Phase IB; Avutometinib; RAS Pathway; Endometrial

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs).

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (2)

Dose Escalation

EXPERIMENTAL

To be administered per dose level during Days 1-21

Drug: Avutometinib; Drug: defactinib; Drug: Everolimus

Dose Expansion

EXPERIMENTAL

To be administered per identified RP2D during Days 1-2

Drug: Avutometinib; Drug: defactinib; Drug: Everolimus

Interventions

Avutometinib DRUG

Given by PO

Dose Escalation; Dose Expansion

defactinib DRUG

Given by PO

Dose Escalation; Dose Expansion

Everolimus DRUG

Given by PO

Dose Escalation; Dose Expansion

Eligibility Criteria

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

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.
• Hepatitis B, or C infection as indicated by detectable viral load. Known to be HIV seropositive 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Verastem, Inc.: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

defactinib; Everolimus

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Shannon N Westin, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shannon N Westin, MD

CONTACT

713-794-4314; swestin@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2025
• First Posted: January 6, 2026
• Study Start (Estimated): June 3, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2030
• Last Updated: January 6, 2026

Record last verified: 2025-12

Locations

US (1)