卡度尼利单抗（PD-1/CTLA-4双特异性抗体）联合化疗治疗抗PD-1耐药的复发或转移性鼻咽癌的疗效和安全性：一项单臂、开放标签的2期试验
Efficacy and safety of cadonilimab (PD-1/CTLA-4 bispecific) in combination with chemotherapy in anti-PD-1-resistant recurrent or metastatic nasopharyngeal carcinoma: a single-arm, open-label, phase 2 trial.
作者信息
Jiang Yaofei, Bei Weixin, Wang Lin, Lu Nian, Xu Cheng, Liang Hu, Ke Liangru, Ye Yanfang, He Shuiqing, Dong Shuhui, Liu Qin, Zhang Chuanrun, Wang Xuguang, Xia Weixiong, Zhao Chong, Huang Ying, Xiang Yanqun, Liu Guoying
机构信息
Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Department of Oncology, The First Affiliated Hospital of Nanchang University, NanChang, China.
出版信息
BMC Med. 2025 Mar 11;23(1):152. doi: 10.1186/s12916-025-03985-4.
BACKGROUND
We aimed to evaluate the efficacy and safety of cadonilimab (anti-PD-1 and CTLA-4 bispecific antibody) plus TPC chemotherapy (NAB-paclitaxel, cisplatin or lobaplatin, and capecitabine) in patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) who failed to PD-1 inhibitor-containing regimens.
METHODS
In this single-arm, open-label, phase 2 study, RM-NPC patients who failed to at least one line of systemic chemotherapy and anti-PD-1 immunotherapy were enrolled and received cadonilimab plus TPC chemotherapy every 3 weeks for up to 6 cycles, followed by cadonilimab plus capecitabine every 3 weeks for a maximum of 2 years. The primary endpoint was the objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DoR), and safety.
RESULTS
Twenty-five patients were enrolled (84% male; median age 44 years (range, 24-60)), with a median follow-up of 10.2 months. The ORR was 68%, with 3 complete responses, 14 partial responses, and 6 stable diseases. The median DoR was 9.1 months (95% CI, 3.8-14.5 months). The median PFS was 10.6 months (95% CI, 5.2-16.0 months). The 12-month OS was 75.6%. Treatment was well tolerated. Grade 3 or 4 treatment-related adverse events occurred in 12 (48%) patients. Fourteen patients (56%) experienced potentially immune-related adverse events (irAEs). One patient experienced a grade 3 immune-related rash and another patient had grade 3 immune-related lipase increased. No treatment-related death occurred.
CONCLUSIONS
Cadonilimab in combination with TPC chemotherapy demonstrated promising antitumoral efficacy and manageable toxicities in patients with RM-NPC who failed frontline immunotherapy. Further trials are warranted to confirm and expand these findings.
TRIAL REGISTRATION
This trial was registered at chictr.org.cn (ChiCTR2200067057).
背景
我们旨在评估卡度尼利单抗（抗程序性死亡蛋白1和细胞毒性T淋巴细胞相关蛋白4双特异性抗体）联合含紫杉烷类的铂类化疗方案（白蛋白结合型紫杉醇、顺铂或洛铂以及卡培他滨）用于对含程序性死亡蛋白1抑制剂方案治疗失败的复发或转移性鼻咽癌（RM-NPC）患者的疗效和安全性。
方法
在这项单臂、开放标签的2期研究中，纳入了对至少一线全身化疗和抗程序性死亡蛋白1免疫治疗失败的RM-NPC患者，每3周接受卡度尼利单抗联合含紫杉烷类的铂类化疗，最多6个周期，随后每3周接受卡度尼利单抗联合卡培他滨治疗，最长2年。主要终点为客观缓解率（ORR）。次要终点包括无进展生存期（PFS）、总生存期（OS）、缓解持续时间（DoR）和安全性。
结果
共纳入25例患者（84%为男性；中位年龄44岁（范围24 - 60岁）），中位随访时间为10.2个月。ORR为68%，其中3例完全缓解，14例部分缓解，6例病情稳定。中位DoR为9.1个月（95%CI，3.8 - 14.5个月）。中位PFS为10.6个月（95%CI，5.2 - 16.0个月）。12个月时的OS为75.6%。治疗耐受性良好。12例（48%）患者发生3级或4级治疗相关不良事件。14例（56%）患者发生潜在的免疫相关不良事件（irAEs）。1例患者发生3级免疫相关皮疹，另1例患者出现3级免疫相关脂肪酶升高。未发生治疗相关死亡。
结论
卡度尼利单抗联合含紫杉烷类的铂类化疗在一线免疫治疗失败的RM-NPC患者中显示出有前景的抗肿瘤疗效和可控的毒性。需要进一步试验来证实和扩展这些发现。
试验注册
本试验在chictr.org.cn上注册（ChiCTR2200067057）。
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