A Phase 1b/2a Study of Pocenbrodib as Monotherapy and in Combination With Darolutamide in Participants With mCRPC

NCT06785636 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: P-300-02-001
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 18

Brief Summary

This is a dose-finding study to assess the safety and preliminary antitumor activity of Pocenbrodib alone or with darolutamide in patients with metastatic castration-resistant prostate cancer (mCRPC)

Conditions

Prostate Cancer; mCRPC (Metastatic Castration-resistant Prostate Cancer)

Keywords

mCRPC, metastatic castrate resistant prostate cancer, prostate cancer,; darolutamide; Pocenbrodib; p300-CBP Transcription Factors

Outcome Measures

Primary Outcomes (4)

• Phase 1b: Confirm the safety and tolerability of pocenbrodib and in combination with darolutamide

  Occurrence and severity of Serious Adverse Events (SAEs) and clinically relevant Adverse Events (AEs), and clinically significant changes in safety laboratory values and electrocardiograms (ECGs)

  28 days

• Phase 1b: Identify the recommended Phase 2 doses of pocenbrodib and in combination with darolutamide

  Frequency and type of DLTs used to determine the maximum tolerated dose (MTD) and RP2Ds

  28 days

• Phase 2a: Assess the safety and tolerability of the RP2Ds of pocenbrodib in combination with darolutamide

  1. Occurrence and severity of SAEs, clinically relevant AEs, and clinically significant changes in safety laboratory values, physical examination (PE) findings, vital signs, and ECGs. 2. Safety and selection of pocenbrodib RP2D for combination with darolutamide for subsequent development

  Through duration of treatment, estimated 6 months

• Phase 2a: Evaluate the efficacy of RP2Ds of pocenbrodib in combination with darolutamide

  Post-177Lu-PSMA-617 (Post-PLUVICTO®) pre-taxane mCRPC: Radiographic progression-free survival (rPFS), assessed as time from randomization to first occurrence of Radiographic progression-free survival (rPFS) according to; i) Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and ii) Prostate Cancer Working Group 3 (PCWG3) criteria or death from any cause, whichever comes first.

  Through duration of treatment, estimated 6 months.

Secondary Outcomes (13)

• Phase 1b: Plasma PK Cmax

  At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first

• Phase 1b: Plasma PK Tmax

  At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first

• Phase 1b: Plasma PK AUC for pocenbrodib

  At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first.

• Phase 1b: Model of cumulative exposure in relation to incidence of adverse events (AEs)

  Through duration of treatment, estimated 6 months.

• Phase 1b: Model of cumulative exposure in relation to incidence of serious adverse events (SAEs)

  Through duration of treatment, estimated 6 months.

Study Arms (4)

Phase 1b Arm 1

EXPERIMENTAL

Pocenbrodib 50-250 mg QD (5 days on/2 days off)

Drug: Pocenbrodib

Phase 1b Arm 2

EXPERIMENTAL

Pocenbrodib 125-150 mg BID monotherapy

Drug: Pocenbrodib

Phase 1b Arm 3

EXPERIMENTAL

Pocenbrodib 125-150 mg BID + darolutamide 600 mg

Drug: Pocenbrodib and Darolutamide

Phase 2a portion

EXPERIMENTAL

Cohort 1: pocenbrodib RP2D-high + darolutamide Cohort 2: pocenbrodib RP2D-low + darolutamide

Drug: Pocenbrodib and Darolutamide

Interventions

Pocenbrodib and Darolutamide DRUG

Pocenbrodib in combination with darolutamide

Phase 1b Arm 3; Phase 2a portion

Pocenbrodib DRUG

Pocenbrodib is a selective oral inhibitor of CBP/p300 bromodomain interaction with acetylated lysines on histones.

Phase 1b Arm 1; Phase 1b Arm 2

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Males with prostate issues
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Current or prior evidence of any small cell or neuroendocrine histology on the most recent prostate biopsy.
• Any liver metastases confirmed by biopsy or evidence of lesions \>1 cm consistent with liver metastases on imaging.
• Intervention with any chemotherapy, investigational agent, or other anticancer drug, including enzalutamide, apalutamide, or darolutamide, 14 days prior to Cycle 1 Day 1 or 5 half-lives (whichever is shorter).
• 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 complications.
• Must have received at least 2 cycles of PLUVICTO®
• line of prior any ARPI therapy
• No prior chemotherapy for mCRPC

Sponsors & Collaborators

• Pathos AI, Inc.: lead
• Duke University: collaborator

Study Sites (18)

MemorialCare Orange Coast Medical Center

Fountain Valley, California, 92708, United States

RECRUITING

Cancer and Blood Research Center

Los Alamitos, California, 90720, United States

RECRUITING

University of Colorado Health

Aurora, Colorado, 80045, United States

RECRUITING

Mount Sinai Medical Center

Miami, Florida, 33140, United States

RECRUITING

Emory University Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Community Health Network

Indianapolis, Indiana, 46250, United States

RECRUITING

Ochsner

Jefferson, Louisiana, 70121, United States

RECRUITING

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Siteman Cancer Center

St Louis, Missouri, 63108, United States

RECRUITING

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

RECRUITING

Duke University medical center

Durham, North Carolina, 27710, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Taylor Cancer Research Center

Maumee, Ohio, 43537, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

Oncology Consultants, P.A

Houston, Texas, 77030, United States

RECRUITING

NEXT Oncology - Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

darolutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Central Study Contacts

Steve Kye, MD, MPH

CONTACT

708-232-3791; clinicaltrials@pathos.com

Study Design

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

Model Details: Phase 1b/2a open-label dose finding study to assess safety, PK, efficacy, PD in patients with mCRPC.

Study Record Dates

• First Submitted: December 10, 2024
• First Posted: January 21, 2025
• Study Start: February 7, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): April 30, 2029
• Last Updated: June 10, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (18)