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

NCT ID: NCT06993844

Last Updated: 2026-01-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

233 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-10

Study Completion Date

2027-12-30

Brief Summary

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

Detailed Description

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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.

Conditions

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Advanced Solid Tumors Advanced Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Fulvestrant
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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

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

Group Type EXPERIMENTAL

ETX-636 dose escalation

Intervention Type DRUG

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.

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

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.

Group Type EXPERIMENTAL

ETX-636 dose escalation in combination with fulvestrant

Intervention Type DRUG

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.

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

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.

Group Type EXPERIMENTAL

ETX-636 dose expansion in combination with fulvestrant

Intervention Type DRUG

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.

Interventions

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ETX-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.

Intervention Type DRUG

ETX-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.

Intervention Type DRUG

ETX-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.

Intervention Type DRUG

Other Intervention Names

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Faslodex Faslodex

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ensem Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States

Site Status RECRUITING

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status RECRUITING

Yale University, Yale Cancer Center

New Haven, Connecticut, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Carolina BioOncology Institute

Huntersville, North Carolina, United States

Site Status RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

START

San Antonio, Texas, United States

Site Status RECRUITING

NEXT

Fairfax, Virginia, United States

Site Status RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Janaki Parameswaran, MD

Role: CONTACT

1-617-383-4993

Melinda Snyder

Role: CONTACT

1-617-383-4993

Facility Contacts

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Angela J Fuller

Role: primary

949-764-4891

Phu Lam

Role: primary

415-818-7994

Carl Brown

Role: primary

203-785-4095

Nicole Ryabin

Role: primary

877-338-7425

Hannah Wall

Role: primary

980-441-1148

Jordi Rodon Ahnert, MD, PhD

Role: primary

713-792-5603

Isabel Jimenenz, RN, MSN

Role: primary

210-593-5265

Maybelle De La Rosa

Role: primary

703-783-4518

Kaysey Hermens

Role: primary

206-667-5715

Other Identifiers

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ETX636-C-001

Identifier Type: -

Identifier Source: org_study_id

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