Phase IBPhase 1NCT07318324
Phase Ib Study of Avutometinib, Defactinib, and Everolimus in RAS Pathway Mutant Endometrial Cancer
A Phase 1 study testing Avutometinib, defactinib and Everolimus in people with Phase IB and Avutometinib, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Phase IB, Avutometinib, RAS Pathway
- What is being tested?
- Avutometinib, defactinib and Everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 13 May 2026to 1 Aug 2030
- Phase
- Phase 1
- 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
None listed.
Who cannot join
- 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.
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- 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
- Specific concurrent ocular disorders:
- History of glaucoma, history of retinal vein occlusion (RVO), predisposing factors for RVO, including uncontrolled hypertension, uncontrolled diabetes
- History of retinal pathology or evidence of visible retinal pathology that is considered a risk factor for RVO, intraocular pressure > 21 mmHg as measured by tonometry, or other significant ocular pathology, such as anatomical abnormalities that increase the risk for RVO.
- Active or chronic, visually significant corneal disorders, other active ocular conditions requiring ongoing therapy, or clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy. Examples of visually significant corneal disorders include corneal degeneration, active or recurrent keratitis, and other forms of serious ocular surface inflammatory conditions. Visually significant corneal disorders do NOT include dry eyes, blepharitis, and uncomplicated corneal erosions.
- Severe skin disorder in the opinion of treating MD that has required systemic therapy within one year of the first dose of study intervention.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Shannon N Westin, MD, 713-794-4314, swestin@mdanderson.org
Shannon N Westin, MD
About this study
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.
Read the detailed description
Primary Objectives To identify the recommended phase 2 dosing (RP2D) of the combination of avutometinib, defactinib and everolimus in participants with recurrent, RAS pathway mutant endometrial cancer.
Secondary Objectives To evaluate the tolerability of the RP2D of avutometinib, defactinib and everolimus including dose limiting toxicities that occur during cycle 1.
- Conditions
- Phase IB, Avutometinib, RAS Pathway, Endometrial
- Being tested
- Avutometinib, defactinib, Everolimus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvutometinibDrug
Given by PO
defactinibDrug
Given by PO
EverolimusDrug
Given by PO
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | To be administered per dose level during Days 1-21 Receives: Drug: Avutometinib; Drug: defactinib; Drug: Everolimus |
| Dose Expansion | Experimental | To be administered per identified RP2D during Days 1-2 Receives: Drug: Avutometinib; Drug: defactinib; Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Through study completion; an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2026
- Study start13 May 2026
- Primary completion1 Aug 2028 (estimated)
- Study completion1 Aug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Phase IBStudies of the same condition, open and under way.
- More trials run by M.D. Anderson 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Verastem, Inc.
- Responsible party
- Sponsor
- Investigators
- Shannon N Westin, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07318324
- Sponsor's protocol ID
- 2025-1174
- Other IDs
- NCI-2025-09476
- Status last verified
- Jun 2026
- First submitted
- 29 Dec 2025
- Last updated
- 29 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Study of Avutometinib, Defactinib, and Everolimus in RAS Pathway Mutant Endometrial Cancer
- ClinicalTrials.gov ID
- NCT07318324
- Acronym / sponsor ID
- 2025-1174
- Conditions
- Phase IB, Avutometinib, RAS Pathway, Endometrial
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 31 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Verastem, Inc.
- Study start
- 13 May 2026 (actual)
- Primary completion
- 1 Aug 2028 (estimated)
- Study completion
- 1 Aug 2030 (estimated)
- First posted
- 6 Jan 2026 (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.
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.
Detailed description
Primary Objectives To identify the recommended phase 2 dosing (RP2D) of the combination of avutometinib, defactinib and everolimus in participants with recurrent, RAS pathway mutant endometrial cancer.
Secondary Objectives To evaluate the tolerability of the RP2D of avutometinib, defactinib and everolimus including dose limiting toxicities that occur during cycle 1.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation | Experimental | Drug: Avutometinib, Drug: defactinib, Drug: EverolimusTo be administered per dose level during Days 1-21 |
| Dose Expansion | Experimental | Drug: Avutometinib, Drug: defactinib, Drug: EverolimusTo be administered per identified RP2D during Days 1-2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (30 listed)
- 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.
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 |
|---|---|---|
| AvutometinibGiven by PO | Drug | Dose Escalation, Dose Expansion |
| defactinibGiven by PO | Drug | Dose Escalation, Dose Expansion |
| EverolimusGiven by PO | Drug | Dose Escalation, Dose Expansion |
Primary outcome
Safety and adverse events (AEs).
Time frame: Through study completion; an average of 1 year
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
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 29 Jun 2026.
- MD Anderson Cancer CenterLink provided by the sponsor.
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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.
Shannon N Westin, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Avutometinib, defactinib and Everolimus in people with Phase IB and Avutometinib, run by M.D. Anderson Cancer Center at 1 site 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 0 inclusion and 30 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: looking for participants now, as of the sponsor's last update on 29 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Contact Shannon N Westin, MD (713-794-4314, swestin@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and adverse events (AEs). (time frame: Through study completion; an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Jun 2026.