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

Phase 2RecruitingNCT06993844

Ensem Therapeutics233 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

233

Conditions

Advanced Solid Tumors Advanced Breast Cancer

Interventions

ETX-636 dose escalationDRUG

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.

ETX-636 dose escalation in combination with fulvestrantDRUG

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.

ETX-636 dose expansion in combination with fulvestrantDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (9)

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States

RECRUITING

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

RECRUITING

Outcomes

Primary Outcomes

Evaluate Safety and Tolerability of ETX-636 monotherapy in Part A and ETX-636 plus fulvestrant combination therapy in Part B

Proportion of participants who experience at least 1 Dose Limiting Toxicity (DLT)

Time frame: 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

Incidence of AEs, treatment discontinuations due to AEs, changes from baseline in laboratory assessments, ECGs and vital signs.

Time frame: 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)

Safety Parameters as described for primary outcomes

Time frame: Average of 6 months

Evaluate efficacy of ETX-636 plus fulvestrant combination therapy at the RP2D(s) in Part C

ORR and CBR according to RECIST v1.1

Time frame: Average of 6 months

Secondary Outcomes

Characterize the Cmax (PK) of ETX-636 monotherapy in Part A and ETX-636 plus fulvestrant combination therapy in Part B

Maximum observed plasma concentration (Cmax) of ETX-636

Time frame: First 2 treatment cycles (each cycle is 28 days)

Characterize the Tmax (PK) of ETX-636 monotherapy in Part A and ETX-636 plus fulvestrant combination therapy in Part B

Calculated time to reach maximum observed plasma concentration of ETX-636

Time frame: First 2 treatment cycles (each cycle is 28 days)

Characterize the AUC (PK) of ETX-636 monotherapy in Part A and ETX-636 plus fulvestrant combination therapy in Part B

Central Contacts

Janaki Parameswaran, MD

CONTACT

1-617-383-4993 janaki.parameswaran@Ensemtx.com

Melinda Snyder

CONTACT

1-617-383-4993 melinda.snyder-ext@Ensemtx.com

Data from ClinicalTrials.gov

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