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

Ensem Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Advanced Solid Tumors; Advanced Breast Cancer

Treatments: Drug: ETX-636 dose expansion in combination with fulvestrant; Drug: ETX-636 dose escalation in combination with fulvestrant; Drug: ETX-636 dose escalation

Study type: Interventional

Funder types: Industry

Identifiers

NCT06993844

ETX636-C-001

Details and patient eligibility

About

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

Full description

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.

Enrollment: 233 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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233 participants in 3 patient groups

Part A Dose Escalation Monotherapy (Advanced Solid Tumors with PIK3CA mutation)

Experimental group

Description:

Part A is a dose escalation monotherapy of ETX-636 in advanced solid tumors with PIK3CA mutation

Treatment:

Drug: ETX-636 dose escalation

Part B Dose Escalation Combination Therapy (HR+/HER2- locally advanced or metastatic breast cancer)

Experimental group

Description:

Part B is a dose escalation combination therapy in HR+/HER2- locally advanced or metastatic breast cancer. The study treatment will be ETX-636, a pan-mutant-selective PI3Kα inhibitor, in combination with fulvestrant (Faslodex) at a fixed dose of 500 mg IM.

Treatment:

Drug: ETX-636 dose escalation in combination with fulvestrant

Part C Dose Expansion Combination Therapy (HR+/HER2- locally advanced or metastatic breast cancer)

Experimental group

Description:

Part B is a dose expansion combination therapy in HR+/HER2- locally advanced or metastatic breast cancer. The study treatment will be ETX-636, a pan-mutant-selective PI3Kα inhibitor, in combination with fulvestrant (Faslodex) at a fixed dose of 500 mg IM.

Treatment:

Drug: ETX-636 dose expansion in combination with fulvestrant