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

NCT06784193 | Recruiting Phase 1 FDA Drug

• 1 other identifier: OP-3136-101
• Study Type: interventional
• Target: 180
• Locations: 2 countries
• Sites: 8

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; Palazestrant

Keywords

KAT6 Inhibitor; Histone Acetyltransferase (HAT) Inhibitor; Epigenetic

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• 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

Study Arms (7)

Part 1A Dose Escalation monotherapy

EXPERIMENTAL

Drug: OP-3136

Part 1B Dose Escalation in combination with fulvestrant

EXPERIMENTAL

Drug: OP-3136; Drug: Fulvestrant

Part 1C Dose Escalation in combination with palazestrant

EXPERIMENTAL

Drug: OP-3136; Drug: Palazestrant

Part 2A Dose Expansion monotherapy - mBC

EXPERIMENTAL

Drug: OP-3136

Part 2A Dose Expansion monotherapy - mCRPC

EXPERIMENTAL

Drug: OP-3136

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

EXPERIMENTAL

Drug: OP-3136; Drug: Fulvestrant; Drug: Palazestrant

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

EXPERIMENTAL

Drug: OP-3136; Drug: Fulvestrant; Drug: Palazestrant

Interventions

OP-3136 DRUG

Selective inhibitor of HAT enzymes KAT6A and KAT6B

Part 1A Dose Escalation monotherapy; Part 1B Dose Escalation in combination with fulvestrant; Part 1C Dose Escalation in combination with palazestrant; Part 2A Dose Expansion monotherapy - mBC; Part 2A Dose Expansion monotherapy - mCRPC; Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 1; Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 2

Fulvestrant DRUG

Selective estrogen receptor degrader (SERD)

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

Palazestrant DRUG

Complete estrogen receptor antagonist (CERAN)

Part 1C Dose Escalation in combination with palazestrant; Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 1; Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 2

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Olema Pharmaceuticals, Inc.: lead

Study Sites (8)

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

RECRUITING

University Medical Center - New Orleans

New Orleans, Louisiana, 70112, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

START - Midwest

Grand Rapids, Michigan, 49546, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

START - San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

START - Mountain Region

West Valley City, Utah, 84119, United States

RECRUITING

Cancer Research South Australia

Adelaide, South Australia, 5000, Australia

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Breast Neoplasms

Interventions

Fulvestrant

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

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

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

CONTACT

415-651-7206; clinical@olema.com

Olema Medical Study Director

CONTACT

Study Design

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

Study Record Dates

• First Submitted: January 14, 2025
• First Posted: January 20, 2025
• Study Start: December 16, 2024
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): August 30, 2027
• Last Updated: October 10, 2025

Record last verified: 2025-09

Locations

AU (1); US (7)