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

Clinicaltrials.gov ID: NCT06785636
db-list-check Status RECRUITING
b-loader Phase PHASE1, PHASE2
b-people Age ≥ 18 Years
b-bullseye-arrow Enrollments 252

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

Drugs

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

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.

Locations

3 locations Found with status Recruiting

Status

  • RECRUITING

Contact Person

  • Samuel Mehr
  • 402-354-8124

Status

  • RECRUITING

Contact Person

  • Julio Peguero, MD
  • 713-600-0900

Status

  • RECRUITING

Contact Person

  • Mohamad Salkeni
  • 571-350-8400

Eligibility 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)

Study Plan

Phase 1 Portion

EXPERIMENTAL

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)

  • DRUG:

    Pocenbrodib

    Description:

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

Phase 2 portion

EXPERIMENTAL

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

  • DRUG:

    Pocenbrodib

    Description:

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

  • DRUG:

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

    Description:

    Pocenbrodib alone or in combination

Outcome Measures

Primary Outcome Measures

Dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D)

Time Frame: 28-day

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.

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.

Secondary Outcome Measures

Maximum Plasma Concentration Observed (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

PSA30

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.

PSA50

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.

PSA90

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.

Progression Free Survival (PFS)

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.

Time to Progression (TTP)

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.

Overall Survival (OS)

Time Frame: From date of first study drug dose until the date of date of death from any cause assessed up to approximately 32 months

Time of Maximum Plasma Concentration Observed (Tmax)

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

Terminal Half-Life (T1/2)

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

Timeline

  • Last Updated
    January 29, 2025
  • Start Date
    January 21, 2025
  • Today
    May 12, 2025
  • Completion Date ( Estimated )
    April 30, 2029

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