RecruitingPhase 1Phase 2NCT06993844

Phase 1/2 Study of ETX-636 in Participants With Advanced Solid Tumors

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

Sponsor

Ensem Therapeutics

Enrollment

233 participants

Start Date

Jun 10, 2025

Study Type

INTERVENTIONAL

Conditions

Advanced Breast Cancer Advanced Solid Tumors

Summary

Phase 1/2, open-label study of ETX-636 in participants with advanced solid tumors

Eligibility

Min Age: 18 Years

Inclusion Criteria7

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.

Exclusion Criteria6

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.

Interventions

DRUGETX-636 dose escalation

ETX-636 is a pan-mutant-selective PI3Kα Inhibitor and degrader in the form of an oral tablet that will be taken once per day in 28-day cycles, to evaluate escalating dose levels.

DRUGETX-636 dose escalation in combination with fulvestrant

ETX-636 is a pan-mutant-selective PI3Kα Inhibitor and degrader in the form of an oral tablet. ETX-636 will be taken in combination with fulvestrant in 28-day cycles, to evaluate escalating dose levels. EXT-636 is an oral tablet that will be taken once per day. Fulvestrant will be administered as an injection 2 weeks apart in the first 28 days, followed by monthly injections.

DRUGETX-636 dose expansion in combination with fulvestrant

ETX-636 is a pan-mutant-selective PI3Kα Inhibitor and degrader in the form of an oral tablet. ETX-636 will be taken in combination with fulvestrant in 28-day cycles, to expand selected dose levels. EXT-636 is an oral tablet that will be taken once per day. Fulvestrant will be administered as an injection 2 weeks apart in the first 28 days, followed by monthly injections.