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

NCT06993844 | Recruiting Phase 1 FDA Drug

• 1 other identifier: ETX636-C-001
• Study Type: interventional
• Target: 233
• Locations: 2 countries
• Sites: 15

Brief Summary

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

Conditions

Advanced Breast Cancer; Advanced Solid Tumors

Keywords

cancer; breast cancer; solid tumors; PIK3CA; PI3Kα inhibitor; Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; HER2-negative breast cancer; HR-positive breast cancer; Gynecologic cancer; Endometrial cancer; Ovarian cancer; Cervical cancer; Head and neck cancer; Head and neck squamous cell carcinoma; Fulvestrant; Antineoplastic Agents; PI3Kα; PI3K alpha; PI3Kα mutation; Alpelisib; Estrogen Receptor Antagonists; Estrogen Antagonists; Hormone Receptor Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; PIK3CA mutation

Outcome Measures

Primary Outcomes (4)

• 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)

  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.

  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

  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

  Average of 6 months

Secondary Outcomes (14)

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

  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

  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

  First 2 treatment cycles (each cycle is 28 days)

• Measure PD effects of ETX-636 monotherapy in Part A and ETX-636 plus fulvestrant combination therapy in Part B and ETX-636 plus fulvestrant at the RP2D(s) in Part C

  First 3 cycles (each cycle is 28 days)

• Changes in fasting blood glucose (All Parts)

  Average of 6 months

Study Arms (3)

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

EXPERIMENTAL

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

Drug: ETX-636 dose escalation

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

EXPERIMENTAL

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.

Drug: ETX-636 dose escalation in combination with fulvestrant

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

EXPERIMENTAL

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.

Drug: ETX-636 dose expansion in combination with fulvestrant

Interventions

ETX-636 dose expansion in combination with fulvestrant 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.

Also known as: Faslodex

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

ETX-636 dose escalation in combination with fulvestrant 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.

Also known as: Faslodex

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

ETX-636 dose escalation 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 A Dose Escalation Monotherapy (Advanced Solid Tumors with PIK3CA mutation)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• \- 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ensem Therapeutics: lead

Study Sites (15)

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

RECRUITING

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

RECRUITING

Yale University, Yale Cancer Center

New Haven, Connecticut, 06520, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

START

San Antonio, Texas, 78229, United States

RECRUITING

NEXT

Fairfax, Virginia, 22031, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Beijing Luhe Hospital,Capital Medical University

Beijing, China

RECRUITING

Fujian Cancer Hospital

Fuzhou, China

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, China

RECRUITING

Shandong Cancer Hospital&Institute

Shandong, China

RECRUITING

Fudan University Shanghai Cancer Hospital

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Neoplasms; Breast Neoplasms; Hereditary Sensory and Autonomic Neuropathies; Neoplasms by Site; Breast Diseases; Endometrial Neoplasms; Ovarian Neoplasms; Uterine Cervical Neoplasms; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Fulvestrant

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Cervical Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study 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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Fulvestrant

Study Record Dates

• First Submitted: May 1, 2025
• First Posted: May 29, 2025
• Study Start: June 10, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (10); CN (5)