Trial launches of CBP/p300 inhibitor in mCRPC

The first patient has been dosed in a phase 1b/2a trial (NCT06785636) of pocenbrodib, a CBP/p300 inhibitor, as a monotherapy and in combination with abiraterone acetate (Zytiga), olaparib (Lynparza), or ¹⁷⁷Lu-PSMA-617 (Pluvicto) in patients with metastatic castration-resistant prostate cancer (mCRPC), Pathos AI announced in a news release.¹

The trial will begin with the phase 1b portion, which will assess pocenbrodib monotherapy at 5 escalating dose levels.

According to the company, pocenbrodib is an oral, small molecule designed to inhibit the proteins CREBBP/EP300 (also known as CBP/p300), which activate genes that promote cancer cell growth and proliferation. The agent (then FT-7051) was previously assessed in the phase 1 COURAGE study (NCT04575766), which showed encouraging safety and pharmacokinetic data in patients with mCRPC, supporting further development in this population.²

"The clinical promise of pocenbrodib, our potential best-in-class CBP/p300 inhibitor, lies not only in its remarkable efficacy in resistant prostate cancer models, but also in our sophisticated biomarker strategy that identifies patients most likely to benefit," said Dr. Jens Renstrup, chief medical officer of Pathos AI, in the news release.¹ "Our precision medicine approach allows us to target the underlying resistance mechanisms to AR-targeted therapy through CBP/p300 inhibition, addressing a significant area of high unmet need for patients with advanced prostate cancer. By integrating multiomic data tied to real-world outcomes to identify specific molecular signatures, our PathOS platform enables us to select the right patients for treatment, potentially improving outcomes in a disease with limited therapeutic options as resistance develops. This study builds on the previously reported data from COURAGE study (NCT04575766) in metastatic castration-resistant prostate cancer and reinforces our confidence in pocenbrodib's potential to improve outcomes for these patients."

Overall, the P300-02-001 study is evaluating the safety, pharmacokinetics, pharmacokinetics, and preliminary anti-tumor activity of pocenbrodib as a monotherapy or in combination with other therapies. In total, the trial plans to enroll 203 adult patients with mCRPC across 3 clinical trial sites in the US.³

Patients eligible for enrollment are those who have progressed on prior therapy and have received at least 1 previous anti-androgen therapy (enzalutamide, apalutamide [Erleada], abiraterone acetate, or darolutamide [Nubeqa]). Patients must also be 18 years of age or older and have histological documentation of prostate adenocarcinoma and metastatic disease based on imaging performed within 56 days prior to screening.

Patients are not eligible for the trial if they have current or prior evidence of any small cell or neuroendocrine histology; any liver metastases on biopsy; intervention with any chemotherapy, investigational agent, or other anticancer drug within 14 days prior to screening; or any other serious condition that may interfere with study participation.

The trial will begin with the phase 1b portion, which will assess pocenbrodib monotherapy at 5 escalating dose levels: 50 mg, 100 mg, 150 mg, 200 mg, and 250 mg once daily with 5 days on and 2 days off. According to the investigators, “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).”

The primary outcome measures include safety, objective response rate, and prostate-specific antigen (PSA) decline. The study will also be used to determine a recommended phase 2 dose of pocenbrodib for combination with abiraterone acetate, olaparib (Lynparza), or ¹⁷⁷Lu-PSMA-617.

The trial will proceed to the phase 2a portion if both acceptable safety and the minimal threshold for efficacy (defined as 30% of patients achieving a PSA decline of at least 50%) are achieved. This phase of the trial will enroll 4 cohorts: pocenbrodib monotherapy (2A) and pocenbrodib in combination with abiraterone acetate (2B), olaparib (2C), and ¹⁷⁷Lu-PSMA-617 (2D).

Primary completion of the study is expected in June 2028.

REFERENCES

1. Pathos AI doses first patient in phase 1b/2a clinical trial of pocenbrodib, a CBP/p300 inhibitor. News release. Pathos AI. Published online and accessed March 20, 2025. https://www.globenewswire.com/news-release/2025/03/20/3046174/0/en/Pathos-AI-Doses-First-Patient-in-Phase-1b-2a-Clinical-Trial-of-Pocenbrodib-a-CBP-p300-Inhibitor.html

2. Armstrong AJ, Gordon MS, Reimers MA, et al. Initial findings from an ongoing first-in-human phase 1 study of the CBP/p300 inhibitor FT-7051 in men with metastatic castration-resistant prostate cancer. Mol Cancer Ther. 2021; 20 (12_Supplement): P202. doi:10.1158/1535-7163.TARG-21-P202

3. Open-label study of pocenbrodib alone and in combination with abiraterone acetate, olaparib, or 177Lu-PSMA-617 (P300). ClinicalTrials.gov. Last updated January 29, 2025. Accessed March 20, 2025. https://clinicaltrials.gov/study/NCT06785636