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

Phase 2RecruitingNCT06785636

Pathos AI, Inc.120 enrolled

Overview

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)

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

120

Conditions

mCRPC (Metastatic Castration-resistant Prostate Cancer)Prostate Cancer

Interventions

PocenbrodibDRUG

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

Pocenbrodib and DarolutamideDRUG

Pocenbrodib in combination with darolutamide

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (18)

MemorialCare Orange Coast Medical Center

Fountain Valley, California, United States

RECRUITING

Outcomes

Primary Outcomes

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)

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: Through duration of treatment, estimated 6 months.

Secondary Outcomes

Phase 1b: Plasma PK Cmax

Plasma PK parameter for 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

Central Contacts

Steve Kye, MD, MPH

CONTACT

708-232-3791 clinicaltrials@pathos.com

Data from ClinicalTrials.gov

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