Abstract：
OBJECTIVE: This study was designed to assess the efficacy and safety of cadonilimab monotherapy, a first-in-class, bi-specific PD-1/CTLA-4 antibody, in patients with previously treated recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC).
METHODS: This multicenter, open-label, single-arm, phase II clinical trial enrolled patients with R/M-NPC who had failed first-line platinum-based chemotherapy and second-line single agent or combined chemotherapy, and immunotherapy-naive. Patients received cadonilimab for 6 mg/kg once every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) in full analysis set (FAS) assessed by investigators according to RECIST v.1.1. The secondary endpoint included progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to response (TTR) and safety.
RESULTS: A total of 23 patients were assessed. The median time from first dose to data cutoff was 16.56 (range, 0.8-25.2) months. ORR was 26.1 % (95 %CI:10.2-48.4). The ORR were 44.4 % (95 %CI: 13.7-78.8) and 14.3 % (95 %CI:1.8-42.8) in patients with tumor PD-L1 expression ≥50 % and <50 %, respectively. ORR was achieved in 40.0 % (95 %CI:12.2-73.8) of patients with EBV-DNA level <4000 IU/ml (n = 10) and 15.4 % (95 %CI:1.9-45.4) of those with ≥4000 IU/ml. The median PFS was 3.71 months (95 %CI: 1.84-9.30). respectively. Median OS was not reached, and the 12-month OS rate was 79.7 % (95 % CI:54.5-91.9). Only two patients (8.3 %) experienced Grade ≥3 treatment-related adverse events (TRAEs) with hypothyroidism (30.4 %), rash (21.7 %) and pruritus (21.7 %) being the most prevalent TRAEs.
CONCLUSIONS: Cadonilimab monotherapy demonstrated a promising efficacy and manageable toxicity in patients with previously treated R-M/NPC and provide an efficacious salvage treatment option.
METHODS: This multicenter, open-label, single-arm, phase II clinical trial enrolled patients with R/M-NPC who had failed first-line platinum-based chemotherapy and second-line single agent or combined chemotherapy, and immunotherapy-naive. Patients received cadonilimab for 6 mg/kg once every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) in full analysis set (FAS) assessed by investigators according to RECIST v.1.1. The secondary endpoint included progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to response (TTR) and safety.
RESULTS: A total of 23 patients were assessed. The median time from first dose to data cutoff was 16.56 (range, 0.8-25.2) months. ORR was 26.1 % (95 %CI:10.2-48.4). The ORR were 44.4 % (95 %CI: 13.7-78.8) and 14.3 % (95 %CI:1.8-42.8) in patients with tumor PD-L1 expression ≥50 % and <50 %, respectively. ORR was achieved in 40.0 % (95 %CI:12.2-73.8) of patients with EBV-DNA level <4000 IU/ml (n = 10) and 15.4 % (95 %CI:1.9-45.4) of those with ≥4000 IU/ml. The median PFS was 3.71 months (95 %CI: 1.84-9.30). respectively. Median OS was not reached, and the 12-month OS rate was 79.7 % (95 % CI:54.5-91.9). Only two patients (8.3 %) experienced Grade ≥3 treatment-related adverse events (TRAEs) with hypothyroidism (30.4 %), rash (21.7 %) and pruritus (21.7 %) being the most prevalent TRAEs.
CONCLUSIONS: Cadonilimab monotherapy demonstrated a promising efficacy and manageable toxicity in patients with previously treated R-M/NPC and provide an efficacious salvage treatment option.
摘要：
目的：本研究旨在评估cadonilimab单药治疗的疗效和安全性，一流的，双特异性PD-1/CTLA-4抗体，在先前治疗过的复发或转移性鼻咽癌（R/M-NPC）患者中。
方法：这个多中心，开放标签，单臂,II期临床试验纳入一线铂类化疗和二线单药或联合化疗失败的R/M-NPC患者，和免疫疗法。患者每2周（Q2W）接受6mg/kg的cadonilimab。主要终点是研究者根据RECISTv.1评估的完整分析集（FAS）中的客观反应率（ORR）。次要终点包括无进展生存期（PFS），总生存期（OS），响应持续时间(DoR)，响应时间（TTR）和安全性。
结果：共评估23例患者。从首次给药到数据截止的中位时间为16.56（范围，0.8-25.2）个月。ORR为26.1%（95CI：10.2-48.4）。肿瘤PD-L1表达≥50％和<50％的患者的ORR分别为44.4％（95CI：13.7-78.8）和14.3％（95CI：1.8-42.8），分别。在EBV-DNA水平<4000IU/ml（n=10）的患者中，ORR达到了40.0％（95CI：12.2-73.8），在≥4000IU/ml的患者中，ORR达到了15.4％（95CI：1.9-45.4）。中位PFS为3.71个月（95CI：1.84-9.30）。分别。未达到OS中位数，12个月OS率为79.7%(95%CI:54.5~91.9)。只有2例患者（8.3%）出现≥3级治疗相关不良事件（TRAEs）伴甲状腺功能减退（30.4%），皮疹(21.7%)和瘙痒(21.7%)是最普遍的TRAE。
结论：Cadonilimab单药治疗在先前治疗过的R-M/NPC患者中显示出有希望的疗效和可控制的毒性，并提供了有效的补救治疗选择。
方法：这个多中心，开放标签，单臂,II期临床试验纳入一线铂类化疗和二线单药或联合化疗失败的R/M-NPC患者，和免疫疗法。患者每2周（Q2W）接受6mg/kg的cadonilimab。主要终点是研究者根据RECISTv.1评估的完整分析集（FAS）中的客观反应率（ORR）。次要终点包括无进展生存期（PFS），总生存期（OS），响应持续时间(DoR)，响应时间（TTR）和安全性。
结果：共评估23例患者。从首次给药到数据截止的中位时间为16.56（范围，0.8-25.2）个月。ORR为26.1%（95CI：10.2-48.4）。肿瘤PD-L1表达≥50％和<50％的患者的ORR分别为44.4％（95CI：13.7-78.8）和14.3％（95CI：1.8-42.8），分别。在EBV-DNA水平<4000IU/ml（n=10）的患者中，ORR达到了40.0％（95CI：12.2-73.8），在≥4000IU/ml的患者中，ORR达到了15.4％（95CI：1.9-45.4）。中位PFS为3.71个月（95CI：1.84-9.30）。分别。未达到OS中位数，12个月OS率为79.7%(95%CI:54.5~91.9)。只有2例患者（8.3%）出现≥3级治疗相关不良事件（TRAEs）伴甲状腺功能减退（30.4%），皮疹(21.7%)和瘙痒(21.7%)是最普遍的TRAE。
结论：Cadonilimab单药治疗在先前治疗过的R-M/NPC患者中显示出有希望的疗效和可控制的毒性，并提供了有效的补救治疗选择。
