China-based urogenital cancer specialist Asieris Pharmaceuticals (SHA: 688176) has announced that it will publish the results of a Phase I clinical study at the American Society of Clinical Oncology (ASCO) annual meeting. The study combines Asieris’ APL-1202 with BeiGene Ltd’s (NASDAQ: BGNE, HKG: 6160) programmed death-1 (PD-1) inhibitor tislelizumab as neoadjuvant chemotherapy (NAC) in muscular invasive bladder cancer (MIBC).
Study Design and Safety Assessment
The study aimed to assess the efficacy and safety of the APL-1202/tislelizumab combination as NAC in MIBC. Enrolling nine subjects in Phase I, the data demonstrated that the combination was safe and tolerable, with no dose-limiting toxicity observed at daily doses of 375mg, 750mg, or 1,125mg of APL-1202. The recommended dose for Phase II clinical trials was set at 1,125mg/day.
Adverse Events and Preliminary Efficacy
A total of six subjects experienced treatment-related adverse events, with one case of CTCAE level 2 electrocardiogram abnormality and one case of CTCAE level 3 liver function abnormality. All other cases were CTCAE level 1, and there were no treatment interruptions, dose reductions, or delays in radical cystectomy due to adverse drug reactions. Preliminary efficacy signals were observed in eight evaluable subjects, with 5/8 (62.5%) having pathological progression below pT2 after radical cystectomy, and 1/8 (12.5%) achieving complete pathological response (pT0).
APL-1202’s Synergistic Effects and Clinical Progress
APL-1202, the world’s first oral and reversible MetAP2 inhibitor to reach the clinic, has shown synergistic effects with a PD-1 inhibitor in bladder cancer pharmacodynamic models. The APL-1202/tislelizumab combination received approval for Phase I/II studies as NAC in MIBC in the US in June 2021 and in China in September the same year. The first patient was enrolled in the Phase II study in December 2022. Additionally, the drug is undergoing Phase III clinical studies in first-line non-muscle invasive bladder cancer (NMIBC) as a monotherapy and as a second-line NMIBC drug combined with chemotherapy.-Fineline Info & Tech
