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

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

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.

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.