Gelonghui May 27 丨 Independent research and development by the companybcgamenodepositbonusClinical research data on the innovative drug HP518 being developed by PROTAC will be released at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The basic situation of the drug HP518 is that the company independently developed an oral, targeted protein degradation chimera (PROTAC) drug for the treatment of patients with advanced prostate cancer (mCRPC).
Clinical data shows that HP518 is a new ARPROTAC degradant that has shown positive efficacy in patients with mCRPC, supporting the next step of clinical research.
Specific clinical data are that this study is the first human, non-randomized, open-label, multicenter Phase 1 dose-escalation study of HP518 in patients with mCRPC to evaluate its safety, tolerability, pharmacokinetics and preliminary drug effectiveness. This study was completed at Peter MacCallum Cancer Centre and other centers in Australia. As of April 22, 2024, a total of 22 patients were enrolled (doses of 25mg-500mg, once a day). The number of patients with ECOG score of 0 at baseline was 10 (45bcgamenodepositbonus.5%), 12 patients (54bcgamenodepositbonus.5%)。The median number of previously treated lines was 3.5 lines (2-6)bcgamenodepositbonus;19 patients (86%) received Enzalumide, 4 patients (18%) received abiraterone;17 patients (77%) received chemotherapy; and 16 patients (73%) received radiotherapy. ctDNA data were obtained for 19 patients and 4 patients had ARLBD mutations. In this study, 3 patients developed PSA50 responses, 2 patients were confirmed to have partial responses (PR) according to the RECIST1.1 criteria, and the efficacy lasted for 36 weeks (subject number 103-003) and 60 weeks (subject number 101-006), respectively. Subject 101-006 showed 80% reduction of liver lesions. The median time to peak plasma concentrations of HP518 after multiple oral doses is 3-12 hours. Over a five-fold dose range (100-500mg), Cmax and AUC0-last increased dose proportional on Day 1, with steady state reaching on Day 56. HP518 has good security characteristics. No dose-limiting toxicities (DLTs) were observed in this study, and a total of 10 serious adverse events (SAEs) were observed, and 1 case of vomiting was related to study drug; 12 cases of Grade ≥3 treatment-emergent adverse events (TEAEs) occurred, and only 1 case of vomiting was related to study drug. The most common AEs are Grade 1 or 2 nausea and vomiting, both of which can be treated with antiemetic drugs.