ETX-636 treatment for advanced PIK3CA-mutant solid tumors and HR+ HER2- breast cancer
A Phase 1/2, Open-label, First-in-human Study of the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ETX-636, a Pan-mutant-selective PI3Kα Inhibitor, as Monotherapy and in Combination With Other Anticancer Therapies in Participants With Advanced Solid Tumors
This will test ETX-636 alone and together with fulvestrant in people with advanced solid tumors that have a PIK3CA mutation, including HR+, HER2- breast cancer.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 233 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Ensem Therapeutics Industry-sponsored |
| Locations | 15 sites (Newport Beach, California and 14 other locations) |
| Trial ID | NCT06993844 on ClinicalTrials.gov |
What this trial studies
This is a Phase 1/2, open-label, multicenter, three-part trial testing escalating doses of the oral PI3Kα inhibitor ETX-636 as monotherapy (Part A) and in combination with fixed-dose fulvestrant (Parts B and C) in participants with advanced solid tumors harboring activating PIK3CA mutations. The trial will first determine safety, tolerability, pharmacokinetics, and pharmacodynamics during dose escalation and then expand the combination cohort in HR+, HER2- locally advanced or metastatic breast cancer. Key eligibility includes measurable disease, ECOG 0-1, adequate organ function, and for the breast cancer cohorts prior CDK4/6 inhibitor and anti-estrogen therapy. Endpoints include dose-limiting toxicities, recommended phase 2 dose, and preliminary anti-tumor activity by RECIST v1.1.
Who should consider this trial
Good fit: Ideal candidates are adults with metastatic or unresectable solid tumors that harbor an activating PIK3CA mutation, have measurable disease and ECOG 0-1, and for Parts B/C have HR+, HER2- breast cancer previously treated with a CDK4/6 inhibitor and anti-estrogen therapy.
Not a fit: Patients without a PIK3CA mutation, those with untreated or uncontrolled CNS metastases, recent distinct malignancies, or insufficient organ function are unlikely to benefit or be eligible for this protocol.
Why it matters
Potential benefit: If successful, ETX-636 could provide a targeted therapy option that shrinks tumors or delays progression in patients with PIK3CA-mutant advanced cancers, including HR+ HER2- breast cancer.
How similar studies have performed: Similar PI3Kα-targeting approaches, notably alpelisib plus fulvestrant, have shown benefit in PIK3CA-mutant HR+ breast cancer, so this trial builds on an established therapeutic strategy while testing a different PI3Kα inhibitor.
Eligibility criteria
Show full inclusion / exclusion criteria
Key Inclusion Criteria: * Metastatic or locally advanced and unresectable solid tumor that has progressed on or after at least one available therapy. * Tumor harboring an activating PIK3CA mutation detected in either tumor tissue or ctDNA. * At least 1 measurable lesion or evaluable disease per RECIST v1.1. * An ECOG performance status score of 0 or 1. * Adequate organ function. Additional key inclusion criterion for Parts B and C: \- Confirmed metastatic or locally advanced HR+/HER2- breast cancer not amenable to surgical resection with curative intent and must have received at least 1 prior CDK4/6 inhibitor and at least 1 prior anti-estrogen therapy. Key Exclusion Criteria: * Has history (within ≤2 years before screening) of a solid tumor or hematological malignancy that is histologically distinct from the cancers being studied. * Has symptomatic brain or spinal metastases or a known or suspected history of untreated or uncontrolled central nervous system (CNS) involvement. * Has an established diagnosis of diabetes mellitus type 1 or has uncontrolled diabetes mellitus type 2. * Has received treatment with any local or systemic anticancer therapy or investigational anticancer agent within 14 days prior to start of treatment. * Has toxicities from previous anticancer therapies that have not resolved to baseline levels with the exception of alopecia and peripheral neuropathy. * Has had radiotherapy outside the target tumor lesions within 14 days prior to start of treatment.
Where this trial is running
Newport Beach, California and 14 other locations
- Hoag Memorial Hospital Presbyterian — Newport Beach, California, United States (Recruiting)
- UCSF Helen Diller Family Comprehensive Cancer Center — San Francisco, California, United States (Recruiting)
- Yale University, Yale Cancer Center — New Haven, Connecticut, United States (Recruiting)
- Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States (Recruiting)
- Dana-Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)
- Carolina BioOncology Institute — Huntersville, North Carolina, United States (Recruiting)
- The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
- Start — San Antonio, Texas, United States (Recruiting)
- Next — Fairfax, Virginia, United States (Recruiting)
- Fred Hutchinson Cancer Center — Seattle, Washington, United States (Recruiting)
- Beijing Luhe Hospital,Capital Medical University — Beijing, China (Recruiting)
- Fujian Cancer Hospital — Fuzhou, China (Recruiting)
- Sun Yat-sen University Cancer Center — Guangzhou, China (Recruiting)
- Shandong Cancer Hospital&Institute — Shandong, China (Recruiting)
- Fudan University Shanghai Cancer Hospital — Shanghai, China (Recruiting)
Study contacts
- Study coordinator: Janaki Parameswaran, MD
- Email: janaki.parameswaran@Ensemtx.com
- Phone: 1-617-383-4993
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.