A Phase 1b/2a, MultiCenter, Open- Label Study of Pocenbrodib as Monotherapy or in Combination With Abiraterone Acetate, Olaparib, or 177Lu-PSMA-617 in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Overview
- Phase
- Phase 1
- Intervention
- Cohort 2A (Pocenbrodib monotherapy), Cohort 2B (Pocenbrodib + abiraterone acetate), Cohort 2C (Pocenbrodib + olaparib), Cohort 2D (Pocenbrodib + 177Lu-PSMA-617
- Conditions
- Not specified
- Sponsor
- Pathos AI, Inc.
- Enrollment
- 252
- Locations
- 30
- Primary Endpoint
- Dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D)
- Status
- Recruiting
- Last Updated
- 8 days ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •≥18 years of age
- •Histologic documentation of prostate adenocarcinoma
- •Metastatic disease, documented by imaging. Imaging performed within 56 days prior to Screening is acceptable
Exclusion Criteria
- •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 Screening or 5 half-live
- •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)
Arms & Interventions
Phase 2 portion
Phase 2 involves Pocenbrodib monotherapy and in combination with abiraterone acetate, olaprib or 177Lu-PSMA0617
Intervention: Cohort 2A (Pocenbrodib monotherapy), Cohort 2B (Pocenbrodib + abiraterone acetate), Cohort 2C (Pocenbrodib + olaparib), Cohort 2D (Pocenbrodib + 177Lu-PSMA-617
Phase 2 portion
Phase 2 involves Pocenbrodib monotherapy and in combination with abiraterone acetate, olaprib or 177Lu-PSMA0617
Intervention: Pocenbrodib
Phase 1 Portion
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)
Intervention: Pocenbrodib
Outcomes
Primary Outcomes
Dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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 Outcomes
- 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)
- 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.)
- 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.)
- 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.)
- 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.)
- 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 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)
- 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)
- 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)