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

Phase 1

Recruiting

• Conditions: mCRPC (Metastatic Castration-resistant Prostate Cancer); Genital Neoplasms, Male; Urogenital Neoplasms; Urogenital Cancers; Prostatic Diseases; Prostatic Neoplasms; Male Urogenital Diseases; Neoplasms; Neoplasms by Site; Prostate Cancer
• Interventions: Drug: Pocenbrodib; Drug: Cohort 2A (Pocenbrodib monotherapy), Cohort 2B (Pocenbrodib + abiraterone acetate), Cohort 2C (Pocenbrodib + olaparib), Cohort 2D (Pocenbrodib + 177Lu-PSMA-617

• Registration Number: NCT06785636
• Lead Sponsor: Pathos AI, Inc.

Brief Summary

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).

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 Timeline

• Study First Submitted: 2024-12-10
• Status Verified: 2025-01
• Study First Submitted QC: 2025-01-20
• Study First Posted: 2025-01-21
• Study Start: 2025-02-07
• Last Update Submitted: 2025-05-19
• Last Update Posted: 2025-05-21
• Primary Completion: 2028-06-30
• Study Completion: 2029-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 252

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 2 portion	Cohort 2A (Pocenbrodib monotherapy), Cohort 2B (Pocenbrodib + abiraterone acetate), Cohort 2C (Pocenbrodib + olaparib), Cohort 2D (Pocenbrodib + 177Lu-PSMA-617	Phase 2 involves Pocenbrodib monotherapy and in combination with abiraterone acetate, olaprib or 177Lu-PSMA0617
Phase 1 Portion	Pocenbrodib	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)
Phase 2 portion	Pocenbrodib	Phase 2 involves Pocenbrodib monotherapy and in combination with abiraterone acetate, olaprib or 177Lu-PSMA0617

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D)	28-day	DLT, serious adverse events (SAEs), clinically relevant adverse events (AEs), and clinically relevant safety laboratory values
RECIST v1.1 objective response rate (ORR)	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.
Prostate specific antigen (PSA)	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.

Secondary Outcome Measures

Name	Time	Method
Maximum Plasma Concentration Observed (Cmax)	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
PSA30	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
PSA50	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
PSA90	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
Progression Free Survival (PFS)	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.
Time to Progression (TTP)	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.
Overall Survival (OS)	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.
Time of Maximum Plasma Concentration Observed (Tmax)	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
Terminal Half-Life (T1/2)	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

Trial Locations

Locations (5)

Siteman Cancer Center; 🇺🇸 St. Louis, Missouri, United States

Duke University medical center; 🇺🇸 Durham, North Carolina, United States

Oncology Consultants, P.A; 🇺🇸 Houston, Texas, United States

Nebraska Cancer Specialists; 🇺🇸 Omaha, Nebraska, United States

NEXT Oncology - Virginia; 🇺🇸 Fairfax, Virginia, United States