Clinical trial NCT06785636: Open-Label Study of Pocenbrodib Alone and in Combination With Abiraterone Acetate, Olaparib, or 177Lu-PSMA-617
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
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
Keywords: mCRPC, metastatic castrate resistant prostate cancer, prostate cancer,
Procenbrodib
castration resistant
Lead sponsor: Pathos AI, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Duke University
First posted: 2025-01-21
Enrollment: 252
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1b/2a open-label dose finding study to assess safety, PK, efficacy, PD in patients with mCRPC.
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D)
timeFrame: 28-day
measure: RECIST v1.1 objective response rate (ORR)
timeFrame: 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.
measure: Prostate specific antigen (PSA)
timeFrame: 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 outcomes:
measure: Maximum Plasma Concentration Observed (Cmax)
timeFrame: At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first
measure: PSA30
timeFrame: 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.
measure: PSA50
timeFrame: 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.
measure: PSA90
timeFrame: 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.
measure: Progression Free Survival (PFS)
timeFrame: 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.
measure: Time to Progression (TTP)
timeFrame: 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.
measure: Overall Survival (OS)
timeFrame: From date of first study drug dose until the date of date of death from any cause assessed up to approximately 32 months
measure: Time of Maximum Plasma Concentration Observed (Tmax)
timeFrame: At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first
measure: Terminal Half-Life (T1/2)
timeFrame: At the end of Cycle 1, 2, 3, and 4 (each cycle is 28 days) or until end of treatment, whichever came first
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Durham
country: United States
facility: Duke University medical center
state: North Carolina
city: Houston
country: United States
facility: Oncology Consultants, P.A
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology - Virginia
state: Virginia
Study officials:
References: