RecruitingRecruiting
Phase 1/2 Study of ETX-636 in Participants With Advanced Solid Tumors
NCT06993844 · Ensem Therapeutics
In plain English
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Official title
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
About this study
Brief Summary: This is a Phase 1/2, open-label, multicenter, 3-part study to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of ETX-636 in participants with advanced solid tumors harboring a PIK3CA mutation.
Part A will evaluate escalating doses of ETX-636 as monotherapy in participants with advanced solid tumors. Part B will evaluate escalating doses of ETX-636 as combination therapy with fixed dose fulvestrant in participants with hormone receptor positive (HR+), HER2 negative (HER2-) locally advanced or metastatic breast cancer. Part C will be a combination therapy expansion in participants with HR+, HER2- locally advanced or metastatic breast cancer.
Each study part will include a 28-day screening period, followed by treatment with ETX-636 monotherapy or combination therapy.
Eligibility 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.
Study design
Enrollment target: 233 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-06-10
Estimated completion: 2027-12-30
Last updated: 2026-05-06
Interventions
Drug: ETX-636 dose escalationDrug: ETX-636 dose escalation in combination with fulvestrantDrug: ETX-636 dose expansion in combination with fulvestrant
Primary outcomes
- • Evaluate Safety and Tolerability of ETX-636 monotherapy in Part A and ETX-636 plus fulvestrant combination therapy in Part B (First 28 days of treatment)
- • Evaluate Safety and Tolerability of ETX-636 monotherapy in Part A and ETX-636 plus fulvestrant combination therapy in Part B (Average of 6 months)
- • Select the Recommended Phase 2 Dose(s) (RP2D) in Part B to be further explored in Part C (combination therapy expansion) (Average of 6 months)
Sponsor
Ensem Therapeutics · industry
Contacts & investigators
ContactJanaki Parameswaran, MD · contact · janaki.parameswaran@Ensemtx.com · 1-617-383-4993
ContactMelinda Snyder · contact · melinda.snyder-ext@Ensemtx.com · 1-617-383-4993
All locations (15)
Hoag Memorial Hospital PresbyterianRecruiting
Newport Beach, California, United States
UCSF Helen Diller Family Comprehensive Cancer CenterRecruiting
San Francisco, California, United States
Yale University, Yale Cancer CenterRecruiting
New Haven, Connecticut, United States
Beth Israel Deaconess Medical CenterRecruiting
Boston, Massachusetts, United States
Dana-Farber Cancer InstituteRecruiting
Boston, Massachusetts, United States
Carolina BioOncology InstituteRecruiting
Huntersville, North Carolina, United States
The University of Texas MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
STARTRecruiting
San Antonio, Texas, United States
NEXTRecruiting
Fairfax, Virginia, United States
Fred Hutchinson Cancer CenterRecruiting
Seattle, Washington, United States
Beijing Luhe Hospital,Capital Medical UniversityRecruiting
Beijing, China
Fujian Cancer HospitalRecruiting
Fuzhou, China
Sun Yat-sen University Cancer CenterRecruiting
Guangzhou, China
Shandong Cancer Hospital&InstituteRecruiting
Shandong, China
Fudan University Shanghai Cancer HospitalRecruiting
Shanghai, China