A Phase 1b/2a Study of Pocenbrodib as Monotherapy and in Combination With Darolutamide in Participants With mCRPC

ClinicalTrials.gov ID

NCT06785636

Lead Sponsor

Pathos AI, Inc.INDUSTRY

Overall Status

Recruiting

Study Type

Interventional

Phase

Phase 1Phase 2

Enrollment

120Estimated

Last Update Posted

Aug 20, 2026Actual

Start Date

Feb 7, 2025Actual

Primary Completion Date

Jun 30, 2028Estimated

Completion Date

Apr 30, 2029Estimated

Official Title

PATHWAY: A Phase 1b/2a, Multicenter, Open- Label Study of Pocenbrodib as Monotherapy and in Combination With Darolutamide in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Brief Summary

This is a dose-finding study to assess the safety and preliminary antitumor activity of Pocenbrodib alone or with darolutamide in patients with metastatic castration-resistant prostate 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 following prior therapy and have been treated with at least 1 potent anti-androgen therapy (enzalutamide, apalutamide, abiraterone acetate, or darolutamide).

Phase 1b is a dose escalation and optimization study of pocenbrodib monotherapy and in combination with darolutamide in order to determine the maximum tolerated dose (MTD) in participants (n=80) and to determine the recommended Phase 2 dose(s) (RP2D(s)).

Phase 1b consists of three arms: Arm 1 (50-250mg QD 5/2), Arm 2 (continuous monotherapy, 125mg-150mg BID), and Arm 3 (continuous combination of pocenbrodib 125-150mg BID + darolutamide 600mg BID), with DRC safety gates governing study progression between arms. Arm 3 is considered the safety run-in for the combination therapy.

Phase 2a is a dose expansion portion of the study to further evaluate the combination of pocenbrodib and darolutamide in participants with mCRPC who have progressed following lutetium-Lu-177-vipivotide-tetraxetan (PLUVICTO) and prior to initiation of taxane-based therapy and will consist of 2 cohorts:

Cohort 1: pocenbrodib RP2D high + darolutamide

Cohort 2: pocenbrodib RP2D low + darolutamide

Safety will be monitored by the DRC

• mCRPC (Metastatic Castration-resistant Prostate Cancer)
• Prostate Cancer

• Pocenbrodib
• Pocenbrodib and Darolutamide

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

Male

Accepts Healthy Volunteers

No

Eligibility Criteria

1b / 2a 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

1b / 2a 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 Cycle 1 Day 1 or 5 half-lives (whichever is shorter).
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 complications.

2a only -key inclusion criteria:

1. Must have received at least 2 cycles of PLUVICTO®
2. 1 line of prior any ARPI therapy
3. No prior chemotherapy for mCRPC

Primary Purpose

Treatment

Allocation

Non-Randomized

Interventional Model

Sequential Assignment

Masking

None (Open Label)

Lead Sponsor

Pathos AI, Inc.INDUSTRY

Collaborators

Duke UniversityOTHER

Yvonne.Enriquez@msmc.com305-674-2625

wsessio@emory.edu404-778-3448

cancerclinicaltrials@bsd.uchicago.edu773-834-7002

Nikkia.lassere@ochsner.org504- 703-0761

314-362-9913

Olivia.Pardi@osumc.edu614-366-8309

(713) 600-0900

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