Phase 1 Study of OP-3136 in Advanced or Metastatic Solid Tumors

A Phase 1 First-in-Human, Open-Label, Multicenter Study of OP-3136 in Adult Participants With Advanced or Metastatic Solid Tumors

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).

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer; Fulvestrant; 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); Palazestrant
• Intervention / Treatment: Drug: Palazestrant; Drug: OP-3136; Drug: Fulvestrant

Detailed Description

Part 1A (Dose Escalation for OP-3136 Monotherapy): This part of the study will evaluate the safety, tolerability, and PK in a range of doses of OP-3136, a lysine acetyltransferases 6A and 6B (KAT6A/B) inhibitor, administered orally once daily to participants with ER+ HER2- advanced or metastatic breast cancer (mBC), advanced or metastatic castration resistant prostate cancer (mCRPC), or advanced or metastatic non-small cell lung cancer (mNSCLC), and determine the maximum tolerated dose (MTD) and the recommended dose/regimen for expansion (RDE).

Part 1B (Dose Escalation for OP-3136 in Combination with Fulvestrant): This part of the study will evaluate the safety and PK of OP-3136 administered in combination with fulvestrant in participants with ER+ HER2- mBC, and determine MTD and RDE for this combination.

Part 1C (Dose Escalation for OP-3136 in Combination with Palazestrant): This part of the study will evaluate the safety and PK of OP-3136 administered in combination with palazestrant in participants with ER+ HER2- mBC, and determine MTD and RDE for this combination.

Part 2A (Dose Expansion for OP-3136 Monotherapy): This part will evaluate two expansion cohorts at the monotherapy RDE from part 1 in participants with ER+ HER2- mBC and participants with mCRPC.

Part 2B (Dose Expansion for OP-3136 in Combination with Fulvestrant OR Palazestrant): This part will evaluate the RDEs for OP-3136 in combination with fulvestrant from Part 1B OR the RDEs of OP-3136 in combination with palazestrant in an expansion cohort in participants with ER+ HER2- mBC.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: There may be multiple sites in this clinical trial Olema Clinical Trial Lead; Phone Number: 415-651-7206; Email: clinical@olema.com
• Study Contact Backup: Name: Olema Medical Study Director

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Cancer Research South Australia
• United States
  • Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Recruiting
      • University Medical Center - New Orleans
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • START - Midwest
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • START - San Antonio
  • Utah
    • West Valley City, Utah, United States, 84119
      • Recruiting
      • START - Mountain Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1A Dose Escalation monotherapy	Drug: OP-3136; Selective inhibitor of HAT enzymes KAT6A and KAT6B
Experimental: Part 1B Dose Escalation in combination with fulvestrant	Drug: OP-3136; Selective inhibitor of HAT enzymes KAT6A and KAT6B; Drug: Fulvestrant; Selective estrogen receptor degrader (SERD)
Experimental: Part 2A Dose Expansion monotherapy - mBC	Drug: OP-3136; Selective inhibitor of HAT enzymes KAT6A and KAT6B
Experimental: Part 2A Dose Expansion monotherapy - mCRPC	Drug: OP-3136; Selective inhibitor of HAT enzymes KAT6A and KAT6B
Experimental: Part 1C Dose Escalation in combination with palazestrant	Drug: Palazestrant; Complete estrogen receptor antagonist (CERAN); Drug: OP-3136; Selective inhibitor of HAT enzymes KAT6A and KAT6B
Experimental: Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 1	Drug: Palazestrant; Complete estrogen receptor antagonist (CERAN); Drug: OP-3136; Selective inhibitor of HAT enzymes KAT6A and KAT6B; Drug: Fulvestrant; Selective estrogen receptor degrader (SERD)
Experimental: Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 2	Drug: Palazestrant; Complete estrogen receptor antagonist (CERAN); Drug: OP-3136; Selective inhibitor of HAT enzymes KAT6A and KAT6B; Drug: Fulvestrant; Selective estrogen receptor degrader (SERD)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum observed concentration (Cmax)	Up to 26 months
Time to maximum concentration (Tmax)	Up to 26 months
Area under the curve from time zero to 24 hours (AUC0-24)	Up to 26 months
Overall Response Rate (ORR)	Up to 26 months
Duration of Response (DOR)	Up to 26 months
Clinical Benefit Rate (CBR)	Up to 26 months

Collaborators and Investigators

• Sponsor: Olema Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2024
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): August 30, 2027

Study Registration Dates

• First Submitted: January 14, 2025
• First Submitted That Met QC Criteria: January 14, 2025
• First Posted (Actual): January 20, 2025

Study Record Updates

• Last Update Posted (Estimated): October 10, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Epigenetic; KAT6 Inhibitor; Histone Acetyltransferase (HAT) Inhibitor
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Skin Diseases; Breast Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Skin and Connective Tissue Diseases; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Fulvestrant
• Other Study ID Numbers: OP-3136-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No