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
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引用次数: 0
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).
期刊介绍：
BMC Medicine is an open access, transparent peer-reviewed general medical journal. It is the flagship journal of the BMC series and publishes outstanding and influential research in various areas including clinical practice, translational medicine, medical and health advances, public health, global health, policy, and general topics of interest to the biomedical and sociomedical professional communities. In addition to research articles, the journal also publishes stimulating debates, reviews, unique forum articles, and concise tutorials. All articles published in BMC Medicine are included in various databases such as Biological Abstracts, BIOSIS, CAS, Citebase, Current contents, DOAJ, Embase, MEDLINE, PubMed, Science Citation Index Expanded, OAIster, SCImago, Scopus, SOCOLAR, and Zetoc.
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