BACKGROUND: Platinum-based doublet chemotherapy regimens, preferentially 
gemcitabine plus cisplatin, are generally considered the first-line standard of 
care for patients with recurrent or metastatic nasopharyngeal carcinoma. 
However, no consensus has been reached regarding treatment following progression 
after first-line therapy. Camrelizumab (SHR-1210) is a humanised anti-programmed 
death-1 (anti PD-1) antibody. We present safety and preliminary antitumour 
activity of camrelizumab alone as second-line therapy in patients with recurrent 
or metastatic nasopharyngeal carcinoma and combined with gemcitabine and 
cisplatin as first-line therapy in this patient population.
METHODS: We report the results from two single-arm, phase 1 trials. Both trials 
included patients aged 18-70 years with histologically or cytologically 
confirmed nasopharyngeal carcinoma and confirmed metastatic disease or 
locoreginal recurrence, and an Eastern Cooperative Oncology Group performance 
status of 0 or 1. Patients who received at least one previous line of treatment 
were enrolled at five academic hospitals in China into the dose-escalation and 
expansion trial to receive camrelizumab monotherapy intravenously at escalating 
doses of 1 mg/kg, 3 mg/kg, and 10 mg/kg, and a bridging dose of 200 mg per dose 
once every 2 weeks (monotherapy trial). Treatment-naive patients were enrolled 
from a single centre in China to receive six cycles of camrelizumab 200 mg (day 
1), gemcitabine 1 g/m2 (days 1 and 8), and cisplatin 80 mg/m2 (day 1) every 3 
weeks followed by camrelizumab 200 mg maintenance once every 3 weeks 
(combination trial). The primary endpoint of both trials was the safety and 
tolerability of the study treatment. Analyses were done per protocol. Both 
trials are registered with ClinicalTrials.gov, number NCT02721589 (camrelizumab 
monotherapy trial) and NCT03121716 (camrelizumab combination trial). Both trials 
are ongoing, but are no longer enrolling patients.
FINDINGS: In the camrelizumab monotherapy trial, between March 31, 2016, and 
Sept 20, 2017, 121 patients were assessed for eligibility, of whom 93 patients 
were enrolled across the dose-escalation and expansion cohorts and received at 
least one dose of camrelizumab (safety population). 15 (16%) of 93 patients had 
treatment-related adverse events of grade 3 or 4, the most common of which were 
elevated conjugated bilirubin concentration (three [3%] of 93 patients), 
stomatitis, anaemia, and increased concentrations of aspartate aminotransferase, 
alanine aminotransferase, and total bilirubin, each of which occurred in two 
(2%) patients. Eight (9%) patients had a treatment-related serious adverse 
event. No dose-limiting toxic effects were observed during the dose-escalation 
phase. 31 (34%; 95% CI 24-44) of 91 evaluable patients on camrelizumab 
monotherapy had an overall response with a median follow-up of 9·9 months (IQR 
8·1-11·7). In the camrelizumab combination trial, between April 18, 2017, and 
Aug 15, 2017, 24 patients were assessed for eligibility, of whom 23 patients 
were enrolled and treated (safety population). 20 (87%) of 23 patients had grade 
3 or 4 treatment-related adverse events: neutropenia (13 [57%] of 23 patients), 
anaemia (11 [48%] patients), leucopenia (11 [48%] patients), thrombocytopenia 
(seven [30%] patients), oedema (two [9%] patients), hyponatraemia (two [9%] 
patients), hypochloraemia (one [4%] patients), and rash (one [4%] patient). Two 
patients had treatment-related serious adverse events. No treatment-related 
deaths occurred in these trials. 20 (91% [95% CI 72-97]) of 22 evaluable 
patients had an overall response with a median follow-up time of 10·2 months 
(IQR 9·7-10·8).
INTERPRETATION: Camrelizumab is a well tolerated, potential treatment option for 
patients with recurrent or metastatic nasopharyngeal carcinoma. The combination 
of camrelizumab plus gemcitabine and cisplatin has a manageable toxicity profile 
and promising preliminary antitumour activity for this disease in 
treatment-naive patients. Randomised controlled trials are needed to further 
establish the role of immune checkpoint inhibition for nasopharyngeal 
carcinomas.
FUNDING: Hengrui Medicine Co, Chinese National Natural Science Foundation 
project, Science and Technology Program of Guangdong, Pearl River Nova Program 
of Guangzhou.