The first patent has been dosed in the phase 1b/2a clinical trial P300-02-001, which is evaluating pocenbrodib alone, and in combination with Zytiga (abiraterone acetate), Lynparza (olaparib) or Pluvicto (177Lu-PSMA-617) in patients with metastatic castration-resistant prostate cancer, according to a news release from manufacturer Patos AI.
"Our precision medicine approach allows us to target the underlying resistance mechanisms to [androgen receptor]-targeted therapy through CBP/p300 inhibition, addressing a significant area of high unmet need for patients with advanced prostate cancer,” Dr. Jens Renstrup, Chief Medical Officer of Patos AI, said in the news release.
The study is expected to enroll approximately 203 patients with metastatic castration-resistant prostate cancer who have progressed despite prior therapy and have been treated with at least one anti-androgen therapy.
The study is currently recruiting at three locations across the United States, in Omaha, Nebraska at Nebraska Cancer Specialists, in Houston, Texas, at Oncology Consultants, and in Fairfax, Virginia, at NEXT Oncology — Virginia.
Glossary:
Objective response rate: percentage of patients who experience a significant reduction in tumor size due to treatment.
PSA decline: measurement of a decrease in prostate-specific antigen (PSA) levels, indicating reduced prostate cancer activity.
Preliminary antitumor activity: early signs of the drug's effectiveness in inhibiting tumor growth or progression, typically measured during Phase 1b/2a trials.
Pharmacokinetics: study of how the drug is absorbed, distributed, metabolized and excreted in the body, providing insight into the drug's action and optimal dosing.
Pharmacodynamics: assessment of the drug's biochemical and physiological effects on the body and its mechanism of action against cancer cells.
Key Inclusion and Exclusion Criteria
Key inclusion criteria for the study includes patients who are 18 years or older, with histologic documentation of prostate adenocarcinoma and metastatic disease, which must be confirmed by imaging. Imaging performed within 56 days prior to screening is acceptable.
Key exclusion criteria include current or prior evidence of any small cell or neuroendocrine histology on the most recent prostate biopsy and any liver metastases confirmed by biopsy or lesions greater than 1 centimeter consistent with liver metastases on imaging. Additionally, participants who have received intervention with any chemotherapy, investigational agent or other anticancer drug, including Xtandi (enzalutamide), Erleada (apalutamide) or Nubeqa (darolutamide) within 14 days prior to screening or five half-lives, whichever is shorter, are excluded.
Participants with any other serious underlying medical, psychiatric, psychological, familial or geographical conditions, as determined by the investigator, that may interfere with study participation and compliance or place the participant at high risk for treatment-related complications are also excluded.
More Study Details and Drug Information
P300-02-001 is a multicenter, open-label, dose-finding phase 1b/2a clinical trial. The study aims to confirm the safety, pharmacokinetics, preliminary antitumor activity and pharmacodynamics of pocenbrodib, both alone and in combination with Zytiga, Lynparza or Pluvicto, in adults with metastatic castration-resistant prostate cancer.
The primary objectives are to assess the safety, objective response rate and PSA decline of pocenbrodib alone and in combination with Zytiga, Lynparza or Pluvicto, and to define a preliminary recommended phase 2 dose of pocenbrodib in combination with these treatments.
“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,” Renstrup continued. “This study builds on the previously reported data from COURAGE study in metastatic castration-resistant prostate cancer and reinforces our confidence in pocenbrodib's potential to improve outcomes for these patients."
Pocenbrodib is an oral, small-molecule inhibitor with the potential to benefit patients with advanced prostate cancer, either alone or with other treatments, according to the release. It works by inhibiting CREBBP/EP300, proteins that activate genes promoting cancer cell growth and proliferation. This inhibition affects the expression of key cancer drivers, including the androgen receptor and its variants, making pocenbrodib relevant to advanced prostate cancer and other cancer indications.
For more information on the trial, use the trial ID, NCT06785636, at clinicaltrials.com.
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