Camrelizumab versus placebo combined with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma: A randomized, double-blind, phase 3 trial.
Authors: Li Zhang, Yunpeng Yang, Song Qu, Jin-Gao Li, Chaosu Hu, Mingjun Xu, Weidong Li, Ting Zhou, Liangfang Shen, Hui Wu, Jin Yi Lang, Guangyuan Hu, Zhanxiong Luo, Zhichao Fu, Shenhong Qu, Ben Zhang, Qing Yang, Xiaojing Zhang, Jianjun Zou, Wenfeng Fang
Journal: Journal of Clinical Oncology (2021)

6000 Background: Camrelizumab plus gemcitabine and cisplatin (GP) showed promising preliminary anticancer activity as first line (1L) therapy in patients (pts) with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) in a phase 1 trial ( W Fang et al; Lancet Oncol 2018). Here, we compared the efficacy and safety of camrelizumab with placebo plus GP as 1L therapy for pts with R/M NPC in a phase 3 trial. Methods: Eligible pts with previously untreated R/M NPC were randomized (1:1) to receive either camrelizumab (200 mg on day 1) plus gemcitabine (1000 mg/m 2 on days 1, 8) and cisplatin (80 mg/m 2 on day 1) or placebo plus the same chemotherapy regimens intravenously Q3W for a maximum of 6 cycles, followed by maintenance therapy with camrelizumab or placebo. The primary end point was progression-free survival (PFS) per independent review committee (IRC). Secondary end points included investigator-assessed PFS, objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS) and tolerability. This trial is registered with ClinicalTrials.gov, number NCT03707509. Results: From Nov 2018 to Nov 2019, 263 pts from 28 centers were randomized to camrelizumab plus GP (n = 134, camrelizumab arm) or placebo plus GP (n = 129, placebo arm). At data cutoff on Dec 31, 2020 (67.7% maturity), 178 IRC-assessed PFS events occurred, and the median follow-up was 15.6 months (range 1.3-25.5). The median PFS per IRC was 10.8 months (95% CI 8.5-13.6) in the camrelizumab arm and 6.9 (95% CI 5.9-7.9) in the placebo arm (HR 0.51 [95% CI 0.37-0.69]; one-sided P &lt; 0.0001). Investigator-assessed PFS showed similar results. IRC-assessed ORR was 88.1% (95% CI 81.3-93.0) in the camrelizumab arm and 80.6% (95% CI 72.7-87.1) in the placebo arm, with a median DOR of 9.9 (95% CI 7.7-12.5) and 5.7 months (95% CI 5.2-6.9; HR 0.48 [95% CI 0.34-0.68]), respectively. The DCR was 96.3% (95% CI 91.5-98.8) in the camrelizumab arm and 94.6% (95% CI 89.1-97.8) in the placebo arm. 18-month PFS rate was 34.8% (95% CI 25.7-44.1) vs 12.7% (95% CI 6.8-20.5), respectively. OS benefit was observed in the camrelizumab arm vs placebo arm (median not reached vs 22.6 months; HR 0.67 [95% CI 0.41-1.11]). Grade ≥3 treatment-related adverse events (TRAEs) occurred in 93% of pts in the camrelizumab arm and 90% in the placebo arm. The most common grade ≥3 TRAEs were decreased white blood cell count (66% vs 70%), decreased neutrophil count (64% vs 65%), decreased platelet count (40% vs 40%), and anemia (39% vs 43%). None of the differences were statistically significant. The safety profile was as expected, with no new signals observed. Conclusions: Addition of camrelizumab to GP significantly prolonged PFS as 1L therapy for R/M NPC, with a manageable safety profile. These data suggest that first line treatment with camrelizumab plus GP could be a standard of care for R/M NPC. Clinical trial information: NCT03707509.