Neoadjuvant PD-1 inhibitor is promising in cutaneous melanoma but remains unknown in acral melanoma (AM). This phase Ib trial study (Clinicaltrials.gov NCT04197882) assessed the efficacy and safety of the combination of neoadjuvant oncolytic virus orienX010 (ori) and anti-PD-1 toripalimab (tori) for resectable AM. Thirty patients of stage III/IV received neoadjuvant therapy of ori and tori for 12 weeks before surgery, followed by adjuvant treatment with tori for 1 year. Primary endpoints were radiographic and pathological response rates, with secondary endpoints of 1- and 2-year recurrence-free survival (RFS) rates, event-free survival (EFS) rates, and safety. Twenty-seven completed surgery and tori adjuvant treatment and median follow-up was 35.7 months. Radiographic and pathological response rates were 36.7% and 77.8%, with complete response rates of 3.3% and 14.8%, 1- and 2-year RFS rates of 85.2% and 81.5%, and 1- and 2-year EFS rates of 83% and 73%, respectively. Adverse events occurred in all patients, mainly grade 1–2. There was no correlation between PET/CT evaluation and pathological response or progression-free survival/overall survival. Patients with pathological response showed tumor beds with high tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs). Cytokines and chemokines analysis showed the combination therapy significantly increases the secretion of proinflammatory cytokines and chemokines in both responders and non-responders. Therefore, neoadjuvant ori and tori demonstrated promising antitumor activity with high response rates and high 2-year RFS/EFS for AM with acceptable tolerability.

新辅助 PD-1 抑制剂在皮肤黑色素瘤中很有前景，但在肢端黑色素瘤 （AM） 中仍不清楚。这项 Ib 期试验研究 （Clinicaltrials.gov NCT04197882） 评估了新辅助溶瘤病毒 orienX010 （ori） 和抗 PD-1 特瑞普利单抗 （tori） 联合治疗可切除 AM 的疗效和安全性。30 例 III/IV 期患者在手术前接受 ori 和 tori 新辅助治疗 12 周，随后接受 tori 辅助治疗 1 年。主要终点是影像学和病理缓解率，次要终点是 1 年和 2 年无复发生存率 （RFS） 、无事件生存率 （EFS） 和安全性。27 例完成手术和 tori 辅助治疗，中位随访时间为 35.7 个月。影像学和病理反应率分别为 36.7% 和 77.8%，完全反应率分别为 3.3% 和 14.8%，1 年和 2 年 RFS 率分别为 85.2% 和 81.5%，1 年和 2 年 EFS 率分别为 83% 和 73%。所有患者均发生不良事件，主要是 1-2 级。PET/CT 评估与病理反应或无进展生存期/总生存期之间没有相关性。有病理反应的患者显示肿瘤床具有高三级淋巴结构 （TLSs） 和肿瘤浸润淋巴细胞 （TIL）。细胞因子和趋化因子分析显示，联合治疗显着增加了反应者和非反应者促炎细胞因子和趋化因子的分泌。因此，新辅助 ori 和 tori 显示出有希望的抗肿瘤活性，具有高反应率和高 2 年 RFS/EFS 对 AM 和可接受的耐受性。