Study of OP-3136 in Advanced or Metastatic Solid Tumors

Phase 1

Recruiting

• 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)
• Interventions: Drug: OP-3136

• Registration Number: NCT06784193
• Lead Sponsor: Olema Pharmaceuticals, Inc.

Brief Summary

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

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

Detailed Description

Part 1 (Dose Escalation): 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 2 (Dose Expansion): This part will evaluate the recommended dose and regimen from Part 1 in the expansion cohorts of participants with ER+ HER2- mBC and participants with mCRPC.

Study Timeline

• Study Start: 2024-12-16
• Study First Submitted: 2025-01-14
• Study First Submitted QC: 2025-01-14
• Study First Posted: 2025-01-20
• Status Verified: 2025-04
• Last Update Submitted: 2025-05-13
• Last Update Posted: 2025-05-15
• Primary Completion: 2027-05-30
• Study Completion: 2027-08-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

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 1 (Dose escalation): 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 2 (Dose Expansion in ER+ HER2- mBC): 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 2 (Dose Expansion in mCRPC): 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).

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

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1 Dose Escalation	OP-3136	-
Part 2 Dose Expansion - mBC	OP-3136	-
Part 2 Dose Expansion - mCRPC	OP-3136	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (7)

Florida Cancer Specialists; 🇺🇸 Sarasota, Florida, United States

University Medical Center - New Orleans; 🇺🇸 New Orleans, Louisiana, United States

START - Midwest; 🇺🇸 Grand Rapids, Michigan, United States

SCRI Oncology Partners; 🇺🇸 Nashville, Tennessee, United States

START - San Antonio; 🇺🇸 San Antonio, Texas, United States

START - Mountain Region; 🇺🇸 West Valley City, Utah, United States

Cancer Research South Australia; 🇦🇺 Adelaide, South Australia, Australia