Abstract：
BACKGROUND: The outcome of patients with resectable mucosal melanoma is poor. Toripalimab combined with axitinib has shown impressive results in metastatic mucosal melanoma with an objective response rate of 48.3% and a median progression-free survival of 7.5 months in a phase Ib trial. It was hypothesized that this combination administered in the neoadjuvant setting might induce a pathologic response in resectable mucosal melanoma, so we conducted this trial.
METHODS: This single-arm phase II trial enrolled patients with resectable mucosal melanoma. Patients received toripalimab 3 mg/kg once every 2 weeks (Q2W) plus axitinib 5 mg two times a day (b.i.d.) for 8 weeks as neoadjuvant therapy, then surgery and adjuvant toripalimab 3 mg/kg Q2W starting 2 ± 1weeks after surgery for 44 weeks. The primary endpoint was the pathologic response rate according to the International Neoadjuvant Melanoma Consortium recommendations.
RESULTS: Between August 2019 and October 2021, 29 patients were enrolled and received treatment, of whom 24 underwent resection. The median follow-up time was 34.2 months (95% confidence interval 20.4-48.0 months). The pathologic response rate was 33.3% (8/24; 4 pathological complete responses and 4 pathological partial responses). The median event-free survival for all patients was 11.1 months (95% confidence interval 5.3-16.9 months). The median overall survival was not reached. Neoadjuvant therapy was tolerable with 8 (27.5%) grade 3-4 treatment-related adverse events and no treatment-related deaths. Tissue samples of 17 patients at baseline and after surgery were collected (5 responders and 12 nonresponders). Multiplex immunohistochemistry demonstrated a significant increase in CD3+ (P = 0.0032) and CD3+CD8+ (P = 0.0038) tumor-infiltrating lymphocytes after neoadjuvant therapy, particularly in pathological responders.
CONCLUSIONS: Neoadjuvant toripalimab combined with axitinib in resectable mucosal melanoma demonstrated a promising pathologic response rate with significantly increased infiltrating CD3+ and CD3+CD8+ T cells after therapy.
METHODS: This single-arm phase II trial enrolled patients with resectable mucosal melanoma. Patients received toripalimab 3 mg/kg once every 2 weeks (Q2W) plus axitinib 5 mg two times a day (b.i.d.) for 8 weeks as neoadjuvant therapy, then surgery and adjuvant toripalimab 3 mg/kg Q2W starting 2 ± 1weeks after surgery for 44 weeks. The primary endpoint was the pathologic response rate according to the International Neoadjuvant Melanoma Consortium recommendations.
RESULTS: Between August 2019 and October 2021, 29 patients were enrolled and received treatment, of whom 24 underwent resection. The median follow-up time was 34.2 months (95% confidence interval 20.4-48.0 months). The pathologic response rate was 33.3% (8/24; 4 pathological complete responses and 4 pathological partial responses). The median event-free survival for all patients was 11.1 months (95% confidence interval 5.3-16.9 months). The median overall survival was not reached. Neoadjuvant therapy was tolerable with 8 (27.5%) grade 3-4 treatment-related adverse events and no treatment-related deaths. Tissue samples of 17 patients at baseline and after surgery were collected (5 responders and 12 nonresponders). Multiplex immunohistochemistry demonstrated a significant increase in CD3+ (P = 0.0032) and CD3+CD8+ (P = 0.0038) tumor-infiltrating lymphocytes after neoadjuvant therapy, particularly in pathological responders.
CONCLUSIONS: Neoadjuvant toripalimab combined with axitinib in resectable mucosal melanoma demonstrated a promising pathologic response rate with significantly increased infiltrating CD3+ and CD3+CD8+ T cells after therapy.
摘要：
背景：可切除的粘膜黑色素瘤患者的预后较差。在1b期试验中，托里帕利马联合阿西替尼在转移性粘膜黑色素瘤中显示出令人印象深刻的结果，客观缓解率为48.3%，中位无进展生存期为7.5个月。据推测，在新辅助治疗中使用的这种组合可能会在可切除的粘膜黑色素瘤中引起病理反应。所以我们进行了这次审判.
方法：这项单臂II期试验纳入了可切除粘膜黑色素瘤患者。患者接受托里帕利马3mg/kgQ2W加阿西替尼5mgBID治疗8周作为新辅助治疗，然后在手术后2±1周开始手术和辅助托里帕利马3mg/kgQ2W，共44周。根据国际新辅助黑色素瘤协会的建议，主要终点是病理反应率。
结果：在2019年8月至2021年10月之间，有29名患者入选并接受了治疗，其中24人接受了切除术。中位随访时间为34.2个月（95%CI[20.4至48.0]）。病理反应率为33.3％（8/24，4pCR，4pPR）。所有患者的中位无事件生存期为11.1个月（95%CI[5.3,16.9]）。未达到OS中位数。新辅助治疗可耐受8例（27.5%）3-4级治疗相关的AE，无治疗相关死亡。收集17名患者在基线和手术后的组织样品(5名应答者和12名非应答者)。多重IHC显示新辅助治疗后CD3+（p=0.0032）和CD3+CD8+（p=0.0038）肿瘤浸润淋巴细胞显着增加，特别是在病理反应者中。
结论：新佐剂托里帕利单抗联合阿西替尼在可切除的粘膜黑色素瘤中表现出良好的病理反应率，治疗后浸润的CD3+和CD3+CD8+T细胞显着增加。
背景：NCT04180995。
方法：这项单臂II期试验纳入了可切除粘膜黑色素瘤患者。患者接受托里帕利马3mg/kgQ2W加阿西替尼5mgBID治疗8周作为新辅助治疗，然后在手术后2±1周开始手术和辅助托里帕利马3mg/kgQ2W，共44周。根据国际新辅助黑色素瘤协会的建议，主要终点是病理反应率。
结果：在2019年8月至2021年10月之间，有29名患者入选并接受了治疗，其中24人接受了切除术。中位随访时间为34.2个月（95%CI[20.4至48.0]）。病理反应率为33.3％（8/24，4pCR，4pPR）。所有患者的中位无事件生存期为11.1个月（95%CI[5.3,16.9]）。未达到OS中位数。新辅助治疗可耐受8例（27.5%）3-4级治疗相关的AE，无治疗相关死亡。收集17名患者在基线和手术后的组织样品(5名应答者和12名非应答者)。多重IHC显示新辅助治疗后CD3+（p=0.0032）和CD3+CD8+（p=0.0038）肿瘤浸润淋巴细胞显着增加，特别是在病理反应者中。
结论：新佐剂托里帕利单抗联合阿西替尼在可切除的粘膜黑色素瘤中表现出良好的病理反应率，治疗后浸润的CD3+和CD3+CD8+T细胞显着增加。
背景：NCT04180995。
