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RecruitingNCT06784193Updated Oct 5, 2026

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

A Phase 1 interventional study of OP-3136 and Fulvestrant in Advanced or Metastatic ER+ HER2- Breast Cancer (mBC), Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) and Advanced or Metastatic Castration-Resistant Prostate Cancer (mCRPC), sponsored by Olema Pharmaceuticals, Inc.. Recruiting at 25 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-05.

Sponsored by Olema Pharmaceuticals, Inc. · Phase 1, Interventional, and Treatment

From the registry’s dates

  • Started Dec 2024; still recruiting 1 year 9 months later.
Updated Oct 5, 2026First sites in 4 new countriesSite recruiting status changed+1 moreGo to Updates ↓
Phase
Phase 1
Study type
Interventional
Enrollment
180
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • 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
03

In context

Carcinoma, Non-Small-Cell Lung

6,488 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,632 are open to participants now.

This study's planned enrollment of 180 is above the median of 62 across 5,213 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.

Browse Carcinoma, Non-Small-Cell Lung studies →

Lead sponsor

Olema Pharmaceuticals, Inc. is the lead sponsor of 6 studies on the registry; 2 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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.

05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
180 participants (estimated)

Study arms

  • Experimental
    Part 1A Dose Escalation monotherapy

    Drug: OP-3136

  • Experimental
    Part 1B Dose Escalation in combination with fulvestrant

    Drug: OP-3136 · Drug: Fulvestrant

  • Experimental
    Part 1C Dose Escalation in combination with palazestrant

    Drug: OP-3136 · Drug: Palazestrant

  • Experimental
    Part 2A Dose Expansion monotherapy - mBC

    Drug: OP-3136

  • Experimental
    Part 2A Dose Expansion monotherapy - mCRPC

    Drug: OP-3136

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

    Drug: OP-3136 · Drug: Fulvestrant · Drug: Palazestrant

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

    Drug: OP-3136 · Drug: Fulvestrant · Drug: Palazestrant

Interventions

  • DrugOP-3136

    Selective inhibitor of HAT enzymes KAT6A and KAT6B

  • DrugFulvestrant

    Selective estrogen receptor degrader (SERD)

  • DrugPalazestrant

    Complete estrogen receptor antagonist (CERAN)

06

What researchers measure

Primary outcomes

  1. Number of participants with dose-limiting toxicities in the Dose Escalation Arms

    Time frame: Up to 28 days

  2. Incidence of adverse events and laboratory abnormalities

    Time frame: Up to 26 months

Secondary outcomes

  1. Maximum observed concentration (Cmax)

    Time frame: Up to 26 months

  2. Time to maximum concentration (Tmax)

    Time frame: Up to 26 months

  3. Area under the curve from time zero to 24 hours (AUC0-24)

    Time frame: Up to 26 months

  4. Overall Response Rate (ORR)

    Time frame: Up to 26 months

  5. Duration of Response (DOR)

    Time frame: Up to 26 months

  6. Clinical Benefit Rate (CBR)

    Time frame: Up to 26 months

07

Study locations

24 of 25 sites recruiting
  • Banner MD Anderson Cancer Center
    Gilbert, Arizona 85234, United States
    Recruiting
  • University of Colorado
    Aurora, Colorado 80045, United States
    Recruiting
  • Florida Cancer Specialists
    Sarasota, Florida 34232, United States
    Recruiting
  • University Medical Center - New Orleans
    New Orleans, Louisiana 70112, United States
    Terminated
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
    Recruiting
  • Dana-Farber Cancer Institute
    Boston, Massachusetts 02215, United States
    Recruiting
  • START - Midwest
    Grand Rapids, Michigan 49546, United States
    Recruiting
  • Memorial Sloan Kettering Cancer Center
    New York, New York 10065, United States
    Recruiting
  • The Ohio State University
    Columbus, Ohio 43021, United States
    Recruiting
  • SCRI Oncology Partners
    Nashville, Tennessee 37203, United States
    Recruiting
  • Tennessee Oncology
    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
  • The Kinghorn Cancer Centre
    Darlinghurst, New South Wales 2010, Australia
    Recruiting
  • Liverpool Hospital
    Liverpool, New South Wales 2170, Australia
    Recruiting
  • Macquarie University Clinical Trials Unit
    Macquarie, New South Wales 2109, Australia
    Recruiting
  • Cancer Research South Australia
    Adelaide, South Australia 5000, Australia
    Recruiting
  • Institut De Cancerologie De L'ouest
    Saint-Herblain, Loire-Atlantique 44805, France
    Recruiting
  • Hôpital Paris Saint-Joseph
    Paris, Paris 75014, France
    Recruiting
  • Institut Gustave Roussy
    Villejuif, Val-de-Marne 94800, France
    Recruiting
  • Queen Mary Hospital
    Hong Kong, Hong Kong, Hong Kong
    Recruiting
  • START Dublin
    Dublin, Dublin D07 R2WY, Ireland
    Recruiting
  • START - Barcelona
    Barcelona, Barcelona 08023, Spain
    Recruiting
  • Start - Fjd
    Madrid, Madrid 28040, Spain
    Recruiting
  • START Madrid - CIOCC
    Madrid, Madrid 28050, Spain
    Recruiting
08

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

09

Updates

1 registry update since Sep 25, 2026
Sites
17 sites added — first sites in France, Hong Kong, Ireland and Spain. University Medical Center - New Orleans is now Terminated
Show 17 added (6 United States, 3 Australia, 3 France, 3 Spain, 1 Hong Kong, 1 Ireland)
  • Banner MD Anderson Cancer Center · Gilbert, United States
  • University of Colorado · Aurora, United States
  • Massachusetts General Hospital · Boston, United States
  • Memorial Sloan Kettering Cancer Center · New York, United States
  • The Ohio State University · Columbus, United States
  • Tennessee Oncology · Nashville, United States
  • The Kinghorn Cancer Centre · Darlinghurst, Australia
  • Liverpool Hospital · Liverpool, Australia
  • Macquarie University Clinical Trials Unit · Macquarie, Australia
  • Institut De Cancerologie De L'ouest · Saint-Herblain, France
  • Hôpital Paris Saint-Joseph · Paris, France
  • Institut Gustave Roussy · Villejuif, France
  • Queen Mary Hospital · Hong Kong, Hong Kong
  • START Dublin · Dublin, Ireland
  • START - Barcelona · Barcelona, Spain
  • Start - Fjd · Madrid, Spain
  • START Madrid - CIOCC · Madrid, Spain
Oct 5, 2026
Show all 1 update
  1. Oct 5, 2026
    17 sites added — first sites in France, Hong Kong, Ireland and Spain. University Medical Center - New Orleans is now Terminated
    Show 17 added (6 United States, 3 Australia, 3 France, 3 Spain, 1 Hong Kong, 1 Ireland)
    • Banner MD Anderson Cancer Center · Gilbert, United States
    • University of Colorado · Aurora, United States
    • Massachusetts General Hospital · Boston, United States
    • Memorial Sloan Kettering Cancer Center · New York, United States
    • The Ohio State University · Columbus, United States
    • Tennessee Oncology · Nashville, United States
    • The Kinghorn Cancer Centre · Darlinghurst, Australia
    • Liverpool Hospital · Liverpool, Australia
    • Macquarie University Clinical Trials Unit · Macquarie, Australia
    • Institut De Cancerologie De L'ouest · Saint-Herblain, France
    • Hôpital Paris Saint-Joseph · Paris, France
    • Institut Gustave Roussy · Villejuif, France
    • Queen Mary Hospital · Hong Kong, Hong Kong
    • START Dublin · Dublin, Ireland
    • START - Barcelona · Barcelona, Spain
    • Start - Fjd · Madrid, Spain
    • START Madrid - CIOCC · Madrid, Spain
    + 1 other change: verification date

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT06784193
Lead sponsor
Olema Pharmaceuticals, Inc.
Responsible party
Sponsor
First posted
Jan 20, 2025
Start date
Dec 16, 2024
Primary completion
May 30, 2027 (estimated)
Completion
Aug 30, 2027 (estimated)
Last update
Oct 5, 2026

Study contacts

There may be multiple sites in this clinical trial Olema Clinical Trial Lead
Contact
clinical@olema.com
415-651-7206
Olema Medical Study Director
Contact

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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