Camrelizumab plus famitinib in patients with recurrent or metastatic nasopharyngeal carcinoma treated with PD-1 blockade: data from a multicohort phase 2 study

Xi Ding; Yi-Jun Hua; Xiong Zou; Xiao-Zhong Chen; Xi-Mei Zhang; Bei Xu; Yan-Feng Ouyang; Zi-Wei Tu; Hui-Feng Li; Chong-Yang Duan; Wei-Jing Zhang; Rui You; You-Ping Liu; Yong-Long Liu; Qi Yang; Pei-Yu Huang; Shu-Ni Wang; Jia Fan; Ming-Yuan Chen

doi:10.1016/j.eclinm.2023.102043

Camrelizumab plus famitinib in patients with recurrent or metastatic nasopharyngeal carcinoma treated with PD-1 blockade: data from a multicohort phase 2 study

EClinicalMedicine. 2023 Jun 23:61:102043. doi: 10.1016/j.eclinm.2023.102043. eCollection 2023 Jul.

Authors

Xi Ding¹, Yi-Jun Hua¹, Xiong Zou¹, Xiao-Zhong Chen², Xi-Mei Zhang³, Bei Xu⁴, Yan-Feng Ouyang¹, Zi-Wei Tu⁵, Hui-Feng Li¹, Chong-Yang Duan⁶, Wei-Jing Zhang⁷, Rui You¹, You-Ping Liu¹, Yong-Long Liu¹, Qi Yang¹, Pei-Yu Huang¹, Shu-Ni Wang⁸, Jia Fan⁹, Ming-Yuan Chen¹

Affiliations

¹ Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
² Department of Head and Neck Tumor Radiotherapy, Cancer Hospital of the University of Chinese Academy of Sciences Zhejiang Cancer Hospital, Hangzhou 310022, China.
³ Department of Radiotherapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin, 300060, China.
⁴ Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
⁵ Department of Radiotherapy, Jiangxi Cancer Hospital, Nanchang 330029, China.
⁶ Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, 510515, China.
⁷ Department of Medical Imaging, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
⁸ Clinical Research & Development, Jiangsu Hengrui Medicine Co., Ltd, Shenyang 110016, China.
⁹ Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Abstract

Background: Treatment options for patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC) are not clear after progression on previous treatment with PD-(L)1 inhibitor; critical gaps in evidence remain for such cases. Immunotherapy combined with antiangiogenic therapy has been reported to have synergistic antitumor activity. Therefore, we evaluated the efficacy and safety of camrelizumab plus famitinib in patients with RM-NPC who failed treatment with PD-1 inhibitor-containing regimens.

Methods: This multicenter, adaptive Simon minimax two-stage, phase II study enrolled patients with RM-NPC refractory to at least one line of systemic platinum-containing chemotherapy and anti-PD-(L)1 immunotherapy. The patient received camrelizumab 200 mg every 3 weeks and famitinib 20 mg once per day. The primary endpoint was objective response rate (ORR), and the study could be stopped early as criterion for efficacy was met (>5 responses). Key secondary endpoints included time to response (TTR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. This trial was registered with ClinicalTrials.gov, NCT04346381.

Findings: Between October 12, 2020, and December 6, 2021, a total of 18 patients were enrolled since six responses were observed. The ORR was 33.3% (90% CI, 15.6-55.4) and the DCR was 77.8% (90% CI, 56.1-92.0). The median TTR was 2.1 months, the median DoR was 4.2 months (90% CI, 3.0-not reach), and the median PFS was 7.2 months (90% CI, 4.4-13.3), with a median follow-up duration of 16.7 months. Treatment-related adverse events (TRAEs) of grade ≥3 were reported in eight (44.4%) patients, with the most common being decreased platelet count and/or neutropenia (n = 4, 22.2%). Treatment-related serious AEs occurred in six (33.3%) patients, and no deaths occurred due to TRAEs. Four patients developed grade ≥3 nasopharyngeal necrosis; two of them developed grade 3-4 major epistaxis, and they were cured by nasal packing and vascular embolization.

Interpretation: Camrelizumab plus famitinib exhibited encouraging efficacy and tolerable safety profiles in patients with RM-NPC who failed frontline immunotherapy. Further studies are needed to confirm and expand these findings.

Funding: Jiangsu Hengrui Pharmaceutical Co., Ltd.

Keywords: Camrelizumab; Famitinib; Nasopharyngeal carcinoma; PD-1 inhibitor; Retreatment; VEGFR.

Associated data

ClinicalTrials.gov/NCT04346381