Hinova Pharmaceuticals (SHA: 688302), a biopharmaceutical company based in China, is scheduled to present data from the first-in-human Phase I clinical study of its drug candidate HP518 at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The study is an open-label, multi-center dose escalation trial designed to evaluate the safety, tolerability, and preliminary efficacy of HP518, an androgen receptor (AR)-targeted PROTAC (PROteolysis TArgeting Chimera) drug for the treatment of metastatic castration-resistant prostate cancer (mCRPC).
As of April 22, 2024, the study enrolled a total of 22 patients, who received daily doses of HP518 ranging from 25mg to 500mg. The patient cohort included 10 patients (45.5%) with a baseline ECOG score of 0 and 12 patients (54.5%) with a score of 1. The median number of prior treatment lines was 3.5 (range: 2-6). After treatment with HP518, 3 patients exhibited a PSA50 response, and 2 patients achieved confirmed partial remission (PR) according to RECIST 1.1 criteria. The duration of efficacy was 36 weeks and 60 weeks, respectively, with one subject experiencing an 80% reduction in liver lesions. The median time to peak blood concentration after multiple oral doses of HP518 was between 3 to 12 hours. The drug showed a good safety profile with no dose limiting toxicity (DLT) observed.
HP518 works by promoting the binding of AR and E3 ligase to form a ternary complex, which leads to the ubiquitination of AR. This process leverages the intracellular ubiquitin proteasome system to degrade AR, reducing the protein expression level of AR in prostate cancer cells and inhibiting the growth of AR-dependent prostate cancer cells, thus offering a potential treatment approach for prostate cancer.- Flcube.com
