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

Pathos AI, Inc.

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Neoplasms by Site; Neoplasms; Male Urogenital Diseases; mCRPC (Metastatic Castration-resistant Prostate Cancer); Urogenital Neoplasms; Prostatic Neoplasms; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Cancers; Prostate Cancer

Treatments: Drug: Cohort 2A (Pocenbrodib monotherapy), Cohort 2B (Pocenbrodib + abiraterone acetate), Cohort 2C (Pocenbrodib + olaparib), Cohort 2D (Pocenbrodib + 177Lu-PSMA-617; Drug: Pocenbrodib

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06785636

P-300-02-001

Details and patient eligibility

About

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).

Full 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.

Enrollment: 252 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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252 participants in 2 patient groups

Phase 1 Portion

Experimental group

Description:

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)

Treatment:

Drug: Pocenbrodib

Phase 2 portion

Experimental group

Description:

Phase 2 involves Pocenbrodib monotherapy and in combination with abiraterone acetate, olaprib or 177Lu-PSMA0617

Treatment:

Drug: Pocenbrodib

Drug: Cohort 2A (Pocenbrodib monotherapy), Cohort 2B (Pocenbrodib + abiraterone acetate), Cohort 2C (Pocenbrodib + olaparib), Cohort 2D (Pocenbrodib + 177Lu-PSMA-617