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
Yaofei Jiang,
Weixin Bei,
Lin Wang,
Nian Lu,
Cheng Xu,
Hu Liang,
Liangru Ke,
Yanfang Ye,
Shuiqing He,
Shuhui Dong,
Qin Liu,
Chuanrun Zhang,
Xuguang Wang,
Weixiong Xia,
Chong Zhao,
Ying Huang,
Yanqun Xiang,
Guoying Liu
Affiliations
Yaofei Jiang
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
Weixin Bei
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
Lin Wang
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
Nian Lu
Department of Radiology, 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
Cheng Xu
Department of Radiotherapy, 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
Hu Liang
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
Liangru Ke
Department of Radiology, 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
Yanfang Ye
Clinical Research Design Division, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
Shuiqing He
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
Shuhui Dong
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
Qin Liu
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
Chuanrun Zhang
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
Xuguang Wang
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
Weixiong Xia
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
Chong Zhao
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
Ying Huang
Department of Radiotherapy, 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
Yanqun Xiang
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
Guoying Liu
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
Abstract 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).
