A Phase 1b/2a Study of Pocenbrodib as Monotherapy and in Combination With Darolutamide in Participants With mCRPC (P300)

PATHWAY: A Phase 1b/2a, Multicenter, Open- Label Study of Pocenbrodib as Monotherapy and in Combination With Darolutamide 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 darolutamide in patients with metastatic castration-resistant prostate cancer (mCRPC)

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; mCRPC (Metastatic Castration-resistant Prostate Cancer)
• Intervention / Treatment: Drug: Pocenbrodib; Drug: Pocenbrodib and Darolutamide

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 following prior therapy and have been treated with at least 1 potent anti-androgen therapy (enzalutamide, apalutamide, abiraterone acetate, or darolutamide).

Phase 1b is a dose escalation and optimization study of pocenbrodib monotherapy and in combination with darolutamide in order to determine the maximum tolerated dose (MTD) in participants (n=80) and to determine the recommended Phase 2 dose(s) (RP2D(s)).

Phase 1b consists of three arms: Arm 1 (50-250mg QD 5/2), Arm 2 (continuous monotherapy, 125mg-150mg BID), and Arm 3 (continuous combination of pocenbrodib 125-150mg BID + darolutamide 600mg BID), with DRC safety gates governing study progression between arms. Arm 3 is considered the safety run-in for the combination therapy.

Phase 2a is a dose expansion portion of the study to further evaluate the combination of pocenbrodib and darolutamide in participants with mCRPC who have progressed following lutetium-Lu-177-vipivotide-tetraxetan (PLUVICTO) and prior to initiation of taxane-based therapy and will consist of 2 cohorts:

Cohort 1: pocenbrodib RP2D high + darolutamide

Cohort 2: pocenbrodib RP2D low + darolutamide

Safety will be monitored by the DRC

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Steve Kye, MD, MPH; Phone Number: 708-232-3791; Email: clinicaltrials@pathos.com

Study Locations

• United States
  • California
    • Fountain Valley, California, United States, 92708
      • Recruiting
      • MemorialCare Orange Coast Medical Center
      • Principal Investigator: Amol Rao, MD
      • Contact: Alexis Wilson; Phone Number: 562-972-8625; Email: awilson4@memorialcare.org
    • Los Alamitos, California, United States, 90720
      • Recruiting
      • Cancer and Blood Research Center
      • Contact: Collin Vu, MD; Phone Number: 714-783-1838; Email: cvu@cbsclinic.com
      • Principal Investigator: Collin Vu, MD
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Health
      • Contact: Peyton Carter; Phone Number: 303-724-9836; Email: PEYTON.CARTER@CUANSCHUTZ.EDU
      • Principal Investigator: Elaine Lam, MD
  • Florida
    • Miami, Florida, United States, 33140
      • Recruiting
      • Mount Sinai Medical Center
      • Contact: Yvonne Enriquez; Phone Number: 305-674-2625; Email: Yvonne.Enriquez@msmc.com
      • Principal Investigator: Bruno Bastos, MD
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University Hospital
      • Contact: Wilena Session; Phone Number: 404-778-3448; Email: wsessio@emory.edu
      • Principal Investigator: Jordan Ciuro
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago
      • Principal Investigator: Mohammad Atiq
      • Contact: Mohammad Atiq, MD; Phone Number: 773-834-7002; Email: cancerclinicaltrials@bsd.uchicago.edu
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Recruiting
      • Community Health Network
      • Principal Investigator: Natraj Ammakkanavar
      • Contact: Office of Research Administration; Phone Number: 317-621-3840; Email: ORA@ecommunity.com
  • Louisiana
    • Jefferson, Louisiana, United States, 70121
      • Recruiting
      • Ochsner
      • Principal Investigator: Brian Halbert
      • Contact: Nikki Lassere; Phone Number: 504- 703-0761; Email: Nikkia.lassere@ochsner.org
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Hospital
      • Principal Investigator: Adel Mandl
      • Contact: Lynn Smith; Phone Number: 410-502-8452; Email: lsmith36@jhmi.edu
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Karmanos Cancer Institute
      • Principal Investigator: Frank Cackowski, MD
      • Contact: Kimberlee Dobson; Phone Number: 313-576-9837; Email: dobsonk@karmanos.org
  • 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: Olivia Pardi; Phone Number: 614-366-8309; Email: Olivia.Pardi@osumc.edu
    • Maumee, Ohio, United States, 43537
      • Recruiting
      • Taylor Cancer Research Center
      • Principal Investigator: John Nemunaitis
      • Contact: Stephanie Ambrose; Phone Number: 567-402-4502; Email: sambrose@tcrcpt.org
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center
      • Principal Investigator: Tian Zhang, MD
      • Contact: Tian Zhang; Phone Number: 833-722-6237; Email: canceranswerline@utsouthwestern.edu
    • 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

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

1b / 2a 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

1b / 2a 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 Cycle 1 Day 1 or 5 half-lives (whichever is shorter).
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 complications.

2a only -key inclusion criteria:

1. Must have received at least 2 cycles of PLUVICTO®
2. 1 line of prior any ARPI therapy
3. No prior chemotherapy for mCRPC

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1b Arm 1; Pocenbrodib 50-250 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 1b Arm 2; Pocenbrodib 125-150 mg BID monotherapy	Drug: Pocenbrodib; Pocenbrodib is a selective oral inhibitor of CBP/p300 bromodomain interaction with acetylated lysines on histones.
Experimental: Phase 1b Arm 3; Pocenbrodib 125-150 mg BID + darolutamide 600 mg	Drug: Pocenbrodib and Darolutamide; Pocenbrodib in combination with darolutamide
Experimental: Phase 2a portion; Cohort 1: pocenbrodib RP2D-high + darolutamide Cohort 2: pocenbrodib RP2D-low + darolutamide	Drug: Pocenbrodib and Darolutamide; Pocenbrodib in combination with darolutamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Occurrence and severity of SAEs, clinically relevant AEs, and clinically significant changes in safety laboratory values, physical examination (PE) findings, vital signs, and ECGs.; 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b: Plasma PK Cmax	Plasma PK parameter for 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	Plasma PK parameter for 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	Plasma PK AUC parameter for pocenbrodib. Pocenbrodib parameters compared to monotherapy Arms 1/2.	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.
Phase 1b: Model of cumulative exposure in relation to incidence of adverse events of special interest (AESIs)		Through duration of treatment, estimated 6 months.
Phase 2a: Characterize the PK of pocenbrodib in combination with darolutamide	Characterize the PK of pocenbrodib in combination with darolutamide in participants with mCRPC after progressing after 177Lu-PSMA-617 (PLUVICTO®) treatment	At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first
Phase 2a: Plasma PK Cmax pocenbrodib/darolutamide	Plasma PK parameter for Cmax for pocenbrodib and darolutamide combined	At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first
Phase 2a: Plasma PK Tmax pocenbrodib/darolutamide	Plasma PK parameter for Tmax for pocenbrodib and darolutamide combined	At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first
Phase 2a: Plasma PK AUC0-24 pocenbrodib/darolutamide	Plasma PK parameter for AUC0-24 for pocenbrodib and darolutamide combined	At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first
Phase 2a: rPFS (radiographic Progression Free Survival)	Evaluate efficacy parameters based on RECIST v1.1 and PCWG3 criteria for rPFS (radiographic Progression Free Survival)	Through duration of treatment, estimated 6 months
Phase 2a: Prostate Specific Antigen (PSA) 50% (PSA50) change from baseline.	Evaluate efficacy parameters based on RECIST v1.1 and PCWG3 criteria for Prostate Specific Antigen (PSA) 50% (PSA50) change from baseline	Through duration of treatment, estimated 6 months
Phase 2a: Prostate Specific Antigen PSA 90% (PSA90) change from baseline.	Evaluate efficacy parameters based on RECIST v1.1 and PCWG3 criteria for Prostate Specific Antigen PSA 90% (PSA90) change from baseline	Through duration of treatment, estimated 6 months

Collaborators and Investigators

• Sponsor: Pathos AI, Inc.
• Collaborators: Duke University

Study record dates

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): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: darolutamide; mCRPC, metastatic castrate resistant prostate cancer, prostate cancer,; p300-CBP Transcription Factors; Pocenbrodib
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Androstenes; Androstanes; darolutamide
• 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