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NCT Number: NCT06993844

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

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

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Key information

Conditions

Advanced Solid Tumors Adnexal Diseases Advanced Breast Cancer Breast Diseases Breast Neoplasms Carcinoma Carcinoma, Squamous Cell Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Endocrine Gland Neoplasms Endocrine System Diseases Endometrial Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Head and Neck Neoplasms Hereditary Sensory and Autonomic Neuropathies Heredodegenerative Disorders, Nervous System Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Nervous System Diseases Nervous System Malformations Neurodegenerative Diseases Neuromuscular Diseases Ovarian Diseases Ovarian Neoplasms Peripheral Nervous System Diseases Polyneuropathies Skin Diseases Skin and Connective Tissue Diseases Squamous Cell Carcinoma of Head and Neck Urogenital Diseases Urogenital Neoplasms Uterine Cervical Diseases Uterine Cervical Neoplasms Uterine Diseases Uterine Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Beijing Luhe Hospital,Capital Medical University, Beijing, China

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

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.

Other names: Faslodex

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.

Other names: Faslodex

Primary outcomes

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

    Time frame: First 28 days of treatment

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

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

    Time frame: Average of 6 months

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

  3. Select the Recommended Phase 2 Dose(s) (RP2D) in Part B to be further explored in Part C (combination therapy expansion)

    Time frame: Average of 6 months

    Safety Parameters as described for primary outcomes

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

    Time frame: Average of 6 months

    ORR and CBR according to RECIST v1.1

Secondary outcomes

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

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

    Maximum observed plasma concentration (Cmax) of ETX-636

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

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

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

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

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

    Calculated area under the plasma concentration curve (AUC) of ETX-636

  4. 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

    Time frame: First 3 cycles (each cycle is 28 days)

    Change from baseline in ctDNA levels; Change from baseline in PD markers in paired biopsies

  5. Changes in fasting blood glucose (All Parts)

    Time frame: Average of 6 months

    Measured by fasting blood glucose

  6. Changes in longitudinal glucose metabolism (All Parts)

    Time frame: Average of 6 months

    Measured by HbA1c

  7. Assess preliminary efficacy of ETX-636 monotherapy in Part A and ETX-636 plus fulvestrant combination therapy in Part B

    Time frame: Average of 6 months

    Objective response rate (ORR) and clinical benefit rate (CBR) based on RECIST v1.1

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

    Time frame: Average of 6 months

    Time to response (TTR) according to RECIST v1.1

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

    Time frame: Average of 6 months

    Duration of response (DoR) according to RECIST v1.1

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

    Time frame: Average of 6 months

    Disease control rate (DCR) according to RECIST v1.1

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

    Time frame: Average of 6 months

    Progression free survival (PFS) according to RECIST v1.1

  12. Evaluate Safety of ETX-636 plus fulvestrant combination therapy at the RP2Ds in Part C

    Time frame: Average of 6 months

    Incidence of adverse events graded according to CTCAE v5.0

  13. Evaluate tolerability of ETX-636 plus fulvestrant combination therapy at the RP2Ds in Part C

    Time frame: Average of 6 months

    Incidence of adverse events graded according to CTCAE v5.0

  14. Characterize the PK of ETX-636 plus fulvestrant using population PK modeling (Part C, to be reported separately)

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

    Plasma concentrations

Study contacts

Contact information is provided by the study sponsor or research team.

Janaki Parameswaran, MD

CONTACT

[email protected]

1-617-383-4993

Melinda Snyder

CONTACT

[email protected]

1-617-383-4993

Sponsors and collaborators

Lead sponsor

Ensem Therapeutics

Industry

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
May 29, 2025
Registry last updated
Jun 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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