Open-Label Study of Pocenbrodib Alone and in Combination With Abiraterone Acetate, Olaparib, or 177Lu-PSMA-617 (P300)

April 22, 2026 updated by: Pathos AI, Inc.

A Phase 1b/2a, MultiCenter, Open- Label Study of Pocenbrodib as Monotherapy or in Combination With Abiraterone Acetate, Olaparib, or 177Lu-PSMA-617 in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

This is a dose-finding study to assess the safety and preliminary antitumor activity of Pocenbrodib alone or with Abiraterone acetate, Olaparib or 177Lu-PSMA-617 in patients with metastatic castration-resistant prostrate cancer (mCRPC).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase 1b/2a multicenter, open-label study to confirm the safety, pharmacokinetics (PK), preliminary antitumor activity, and pharmacodynamics (PD) of pocenbrodib for the treatment of participants with mCRPC who have progressed despite prior therapy and have been treated with at least 1 potent anti-androgen therapy (enzalutamide, apalutamide, abiraterone acetate, or darolutamide).

The Phase 1b portion of the study involves pocenbrodib monotherapy at multiple, sequential five rising doses (50, 100, 150, 200, and 250mg) initially using a QD dosing schedule of 5 days on/2 days off. The first dose level (50 mg) will enroll at least 3 participants (with 3 more added if the first 3 participants yield 1 dose-limiting toxicity). Once safety is confirmed through Data Review Committee (DRC), the next higher pocenbrodib dose level cohort can begin enrollment.

If both acceptable safety and minimal threshold of efficacy (predefined as 30% PSA50 are achieved, the sponsor will proceed to Phase 2a.

Phase 2a will enroll participants in each of 4 cohorts: pocenbrodib monotherapy (2A), and 3 combination therapy cohorts: pocenbrodib + abiraterone acetate (2B), pocenbrodib + olaparib (2C), and pocenbrodib + 177Lu-PSMA-617 (2D). All cohorts may enroll in parallel, but each cohort will be evaluated independently for safety and efficacy.

Study Type

Interventional

Enrollment (Estimated)

252

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Fountain Valley, California, United States, 92708
        • Recruiting
        • MemorialCare Orange Coast Medical Center
        • Principal Investigator:
          • Amol Rao, MD
        • Contact:
      • Los Alamitos, California, United States, 90720
        • Recruiting
        • Cancer and Blood Research Center
        • Contact:
        • Principal Investigator:
          • Collin Vu, MD
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Health
        • Contact:
        • Principal Investigator:
          • Elaine Lam, MD
    • Florida
      • Miami, Florida, United States, 33140
        • Recruiting
        • Mount Sinai Medical Center
        • Contact:
        • Principal Investigator:
          • Bruno Bastos, MD
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University Hospital
        • Contact:
        • Principal Investigator:
          • Jordan Ciuro
    • Illinois
      • Chicago, Illinois, United States, 60637
    • Indiana
      • Indianapolis, Indiana, United States, 46250
        • Recruiting
        • Community Health Network
        • Principal Investigator:
          • Natraj Ammakkanavar
        • Contact:
    • Louisiana
      • Jefferson, Louisiana, United States, 70121
        • Recruiting
        • Ochsner
        • Principal Investigator:
          • Brian Halbert
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins Hospital
        • Principal Investigator:
          • Adel Mandl
        • Contact:
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Karmanos Cancer Institute
        • Principal Investigator:
          • Frank Cackowski, MD
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63108
        • Recruiting
        • Siteman Cancer Center
        • Principal Investigator:
          • Melissa Reimers, MD
        • Contact:
          • Hannah Black
          • Phone Number: 314-362-9913
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Recruiting
        • Nebraska Cancer Specialists
        • Principal Investigator:
          • Ralph Hauke, MD
        • Contact:
          • Evan Roberts
          • Phone Number: 531-329-3652
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Medical Center
        • Principal Investigator:
          • Andrew Armstrong, MD
        • Contact:
          • Blayne Carney
          • Phone Number: 9196608015
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University
        • Principal Investigator:
          • Lingbin Meng
        • Contact:
      • Maumee, Ohio, United States, 43537
        • Recruiting
        • Taylor Cancer Research Center
        • Principal Investigator:
          • John Nemunaitis
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • University of Texas Southwestern Medical Center
        • Principal Investigator:
          • Tian Zhang, MD
        • Contact:
      • Houston, Texas, United States, 77030
        • Recruiting
        • Oncology Consultants, P.A
        • Principal Investigator:
          • Julio Peguero, MD
        • Contact:
          • Julio Peguero
          • Phone Number: (713) 600-0900
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Next Oncology - Virginia
        • Principal Investigator:
          • Mohamad Salkeni, MD
        • Contact:
          • Blake Patterson
          • Phone Number: 703-783-4505

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  1. ≥18 years of age
  2. Histologic documentation of prostate adenocarcinoma
  3. Metastatic disease, documented by imaging. Imaging performed within 56 days prior to Screening is acceptable

Key Exclusion Criteria:

  1. Current or prior evidence of any small cell or neuroendocrine histology on the most recent prostate biopsy
  2. Any liver metastases confirmed by biopsy or evidence of lesions >1 cm consistent with liver metastases on imaging
  3. Intervention with any chemotherapy, investigational agent, or other anticancer drug, including enzalutamide, apalutamide, or darolutamide, 14 days prior to Screening or 5 half-live20.
  4. Any other serious underlying medical, psychiatric, psychological, familial, or geographical condition, which in the judgment of the Investigator may interfere with study participation and compliance or place the participant at high risk from treatment-related complicationss from the last dose (whichever is shorter)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1 Portion
Dose level 1: 50 mg QD (5 days on/2 days off) Dose level 2: 100 mg QD (5 days on/2 days off) Dose level 3: 150 mg QD (5 days on/2 days off) Dose level 4: 200 mg QD (5 days on/2 days off) Dose level 5: 250 mg QD (5 days on/2 days off)
Drug: Pocenbrodib
Pocenbrodib is a selective oral inhibitor of CBP/p300 bromodomain interaction with acetylated lysines on histones.
Experimental: Phase 2 portion
Phase 2 involves Pocenbrodib monotherapy and in combination with abiraterone acetate, olaprib or 177Lu-PSMA0617
Drug: Pocenbrodib
Pocenbrodib is a selective oral inhibitor of CBP/p300 bromodomain interaction with acetylated lysines on histones.
Drug: Cohort 2A (Pocenbrodib monotherapy), Cohort 2B (Pocenbrodib + abiraterone acetate), Cohort 2C (Pocenbrodib + olaparib), Cohort 2D (Pocenbrodib + 177Lu-PSMA-617
Pocenbrodib alone or in combination

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D)
Time Frame: 28-day
DLT, serious adverse events (SAEs), clinically relevant adverse events (AEs), and clinically relevant safety laboratory values
28-day
RECIST v1.1 objective response rate (ORR)
Time Frame: From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.
Proportion of participants with ORR. The response rate will be reported with an exact 95% CI.
From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.
Prostate specific antigen (PSA)
Time Frame: From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.
PSA decline post-treatment = ≥ 30% PSA50. The PSA will be reported with an exact 95% CI.
From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Plasma Concentration Observed (Cmax)
Time Frame: At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first
Characterize the Cmax of pocenbrodib in men with mCRPC
At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first
PSA30
Time Frame: From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.
30% decrease from baseline in PSA while on treatment
From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.
PSA50
Time Frame: From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.
50% decrease from baseline in PSA while on treatment
From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.
PSA90
Time Frame: From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.
90% decrease from baseline in PSA while on treatment
From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.
Progression Free Survival (PFS)
Time Frame: From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.
Radiographic PFS is defined as the time from the first date of pocenbrodib administration to the date of radiographic disease progression as outlined in PCWG3 guidelines or death from any cause.
From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.
Time to Progression (TTP)
Time Frame: From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.
Time to radiographic PFS is defined as the time from the first date of pocenbrodib administration to the date of radiographic disease progression as outlined in PCWG3 guidelines or death from any cause.
From date of enrollment until the date of first documented progression as per PCWG3 criteria, without ongoing clinical benefit or unacceptable toxicity or date of death from any cause, which came first, estimated to be 6 months.
Overall Survival (OS)
Time Frame: From date of first study drug dose until the date of date of death from any cause assessed up to approximately 32 months
OS is defined as the time from the first date of pocenbrodib administration until death from any cause.
From date of first study drug dose until the date of date of death from any cause assessed up to approximately 32 months
Time of Maximum Plasma Concentration Observed (Tmax)
Time Frame: At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first
Characterize the Tmax of pocenbrodib in men with mCRPC
At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first
Terminal Half-Life (T1/2)
Time Frame: At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first
Characterize the T 1/2 of pocenbrodib in men with mCRPC
At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pathos AI, Inc.

Collaborators

Duke University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 7, 2025

Primary Completion (Estimated)

June 30, 2028

Study Completion (Estimated)

April 30, 2029

Study Registration Dates

First Submitted

December 10, 2024

First Submitted That Met QC Criteria

January 20, 2025

First Posted (Actual)

January 21, 2025

Study Record Updates

Last Update Posted (Actual)

April 24, 2026

Last Update Submitted That Met QC Criteria

April 22, 2026

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P-300-02-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Pathos AI, Inc. will determine once safety and preliminary efficacy is defined.

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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