Abstract CT099: First-in-human study of ALF501, polypeptide PSMA-targeted chimeric antigen receptor engineered natural killer cells) for castration-resistant prostate cancer

Abstract

Abstract Abstract Background: The mortality of castration-resistant prostate cancer (CRPC) is high due to lack of an effective treatment. Chimeric antigen receptor (CAR) based therapy is a promising immunotherapeutic strategy. In preclinical models, we established ALF501, a novel CAR-NK cells with both a high affinity for PSMA and a clinically significant tumoricidal effect on CRPC. Here we report the results from the first-in-human case of ALF501 for CRPC. Methods: In this study, ALF501was dosed intravenous for a total of three courses, with an interval of 3 months, each infusion of 5 × 108 cells, and 3 consecutive days of infusion as a course of treatment. Observation continued until progression or unacceptable toxicity for up to 1 years. Primary objectives were safety and tolerability; secondary objectives included preliminary antitumor activity. Results: An 80-year-old man who underwent laparoscopic radical prostatectomy in February 2018 and developed a relapse in April 2021. Starting with July 16 2021, he received three courses of ALF501. No liver and kidney toxicity was observed, and the safety profile was good. Progression-free survival was 12months as of April 23, 2022, during which PSA decreased by 97.5% from baseline. Imaging follow-up showed that the tumor was stable, and chest CT showed that the original pleural effusion and pericardial effusion disappeared, and the high-density shadow previously considered osteogenic bone metastasis was reduced overall. Conclusions: ALF501 is safe and feasible for the treatment of CRPC, and has preliminary anti-tumor efficacy. This is a case study, and it is necessary to expand the patient sample size in the future to confirm whether there is a difference in efficacy for different patients. Citation Format: Hui Shi, Yanan Lin, Jie Ran, Yan Jin, Shengbang Zhang, Qi Wang, Huiyuan Zhang, Lida Wu, Yuchun Gu, Shengjiang Tan, Yao Wang. First-in-human study of ALF501, polypeptide PSMA-targeted chimeric antigen receptor engineered natural killer cells) for castration-resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT099.