Phase IIa Trial of Locoregional High-Dose Autologous Natural Killer Cell Therapy Combined with Hepatic Arterial Infusion Chemotherapy for Locally Advanced Hepatocellular Carcinoma.
Abstract
Purpose Hepatocellular carcinoma (HCC) refractory to locoregional therapies remains a major clinical challenge. This study evaluated the efficacy and safety of locoregional high-dose autologous natural killer (NK) cell therapy combined with hepatic arterial infusion chemotherapy (HAIC) in patients with locally advanced HCC. Materials and Methods This open-label, multicenter, phase IIa study enrolled patients with locally advanced HCC refractory to standard care. Patients achieving stable disease (SD) or better after two HAIC cycles (5-fluorouracil and cisplatin) underwent two additional HAIC cycles followed by hepatic arterial NK cell infusion for up to two cycles. The primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR). Secondary endpoints included investigator-assessed ORR, disease control rate (DCR), duration of response (DOR), time to progression (TTP), overall survival (OS), safety, and immunologic response. Tumor response was assessed per modified RECIST for HCC. Results Of 17 enrolled patients, 16 were evaluable. IRC-assessed ORR was 68.75% (exact 95% confidence interval, 41.34-88.98) [complete response (CR): 18.75%; partial response (PR): 50.00%], and investigator-assessed ORR was 62.50%. Both assessments yielded a DCR of 100%. Median DOR was 12.65 and 10.48 months by IRC and investigator assessment, respectively. Median investigator-assessed TTP was 16.82 months; IRC-assessed TTP was not reached. Median OS was 24.05 months. No severe NK cell-related toxicities were observed. Conclusion Locoregional high-dose autologous NK cell therapy following HAIC showed promising antitumor activity and an acceptable profile in selected patients with locally advanced HCC. These findings warrant validation in randomized trials designed to isolate the incremental contribution of NK cell therapy.