Recruiting
Phase 1

OP-3136

Sponsor:

Olema Pharmaceuticals, Inc.

Code:

NCT06784193

Conditions

Advanced or Metastatic ER+ HER2- Breast Cancer (mBC)

Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Advanced or Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Metastatic Breast Cancer

Fulvestrant

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

OP-3136

Fulvestrant

Palazestrant

Study Details

Brief summary:

This is a first-in-human, open-label, multicenter phase 1 study to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of OP-3136, a lysine acetyltransferases 6A and 6B (KAT6A/B) inhibitor, as monotherapy and in combination with other anticancer agents in participants with advanced solid tumors.

This study consists of 2 parts: a dose escalation part (Part 1) and dose expansion part (Part 2).

Conditions

Advanced or Metastatic ER+ HER2- Breast Cancer (mBC)

Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Advanced or Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Metastatic Breast Cancer

Fulvestrant

Study ID

NCT06784193

Start date

Dec 16, 2024

Status verified date

Sep, 2025

Completion date

Aug 30, 2027

Anticipated

Primary completion date

May 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Key Inclusion Criteria:

  • Participants with advanced or metastatic ER+HER2- breast cancer, mCRPC, or NSCLC (Part 1) or advanced or metastatic ER+HER2- BC or mCRPC (Part 2).
  • Part 1A (Dose escalation for OP-3136 monotherapy): Participants must have a tumor that is unresectable or metastatic and for which life prolonging measures do not exist or available therapies are intolerable or no longer effective.
  • Part 1B (Dose escalation for OP-3136 in combination with fulvestrant): Participants with advanced or metastatic ER+ HER2- breast cancer that have progressed on or after at least 1 prior line of treatment that included endocrine therapy and CDK 4/6 inhibitor in advanced or metastatic setting and must have received no more than 2 prior lines of endocrine therapy (one of which must be in combination with CDK4/6 inhibitor) and no more than 1 prior line of chemotherapy or an antibody-drug conjugate in the advanced or metastatic setting.
  • Part 1C (Dose escalation for OP-3136 in combination with palazestrant): Participants with advanced or metastatic ER+ HER2- breast cancer that have progressed on or after at least 1 prior line of treatment that included endocrine therapy and CDK 4/6 inhibitor in advanced or metastatic setting and must have received no more than 2 prior lines of endocrine therapy (one of which must be in combination with CDK4/6 inhibitor) and no more than 1 prior line of chemotherapy or an antibody-drug conjugate in the advanced or metastatic setting.
  • Part 2A (Dose Expansion in ER+ HER2- mBC for OP-3136 monotherapy): Participants must have received up to 3 prior lines of endocrine therapy (one of which must be in combination with CDK4/6 inhibitor) and up to 1 prior line of chemotherapy or an antibody-drug conjugate.
  • Part 2A (Dose Expansion in mCRPC for OP-3136 monotherapy): Participants must have received up to 4 lines of prior systemic therapy for prostate cancer. Prior therapy must include treatment with an androgen receptor pathway inhibitor(s).
  • Part 2B (Dose Expansion in ER+ HER2- mBC for OP-3136 in combination with fulvestrant OR Dose Expansion in ER+ HER2- mBC for OP-3136 in combination with palazestrant): Participants must have progressed on or after at least 1 prior line of treatment that included endocrine therapy and CDK 4/6 inhibitor in advanced or metastatic setting. Participants must have received no more than 2 prior lines of endocrine therapy in the advanced or metastatic setting and no more than 1 prior line of chemotherapy or an antibody-drug conjugate in the advanced or metastatic setting.

Key Exclusion Criteria:

  • Prior therapy with KAT6A/B inhibitor in any treatment setting.
  • Participants with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term.
  • Known active or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, leptomeningeal disease, or a spinal cord compression that require CNS-specific treatment, or participants who did not demonstrate clinical and radiologic stability during the last 2 months prior to the first dose of study treatment or require or are currently on steroid therapy for CNS metastases.
  • History of cerebral vascular disease, including transient ischemic attack, within 6 months prior to the first dose of study treatment.
  • History of or ongoing impaired cardiac function or clinically significant cardiac disease within 6 months prior to the first dose of study treatment.

Note: Additional inclusion/exclusion criteria may apply.

Study Design

Enrollment

180 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part 1A Dose Escalation monotherapy

experimental: Part 1B Dose Escalation in combination with fulvestrant

experimental: Part 1C Dose Escalation in combination with palazestrant

experimental: Part 2A Dose Expansion monotherapy - mBC

experimental: Part 2A Dose Expansion monotherapy - mCRPC

experimental: Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 1

experimental: Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 2

Interventions

OP-3136

Selective inhibitor of HAT enzymes KAT6A and KAT6B

Fulvestrant

Selective estrogen receptor degrader (SERD)

Palazestrant

Complete estrogen receptor antagonist (CERAN)

Primary outcome measure

  • Number of participants with dose-limiting toxicities in the Dose Escalation Arms [ Time Frame: Up to 28 days ]
  • Incidence of adverse events and laboratory abnormalities [ Time Frame: Up to 26 months ]

Central Contacts and Locations

Central contacts

There may be multiple sites in this clinical trial Olema Clinical Trial Lead

415-651-7206clinical@olema.com

Locations

Florida Cancer Specialists

Recruiting

Sarasota, Florida, United States, 34232

University Medical Center - New Orleans

Recruiting

New Orleans, Louisiana, United States, 70112

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

START - Midwest

Recruiting

Grand Rapids, Michigan, United States, 49546

SCRI Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

START - San Antonio

Recruiting

San Antonio, Texas, United States, 78229

START - Mountain Region

Recruiting

West Valley City, Utah, United States, 84119

More Information

Sponsor

Olema Pharmaceuticals, Inc.

Last update posted

Oct 10, 2025

Last verified

Sep, 2025

Keywords

  • KAT6 Inhibitor
  • Histone Acetyltransferase (HAT) Inhibitor
  • Epigenetic

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Olema Pharmaceuticals, Inc. on 2025-10-10.