PURPOSE: As yet, no checkpoint inhibitor has been approved to treat 
nasopharyngeal carcinoma (NPC). This study was aimed to evaluate the antitumor 
activity, safety, and biomarkers of toripalimab, a new programmed death-1 (PD-1) 
inhibitor for recurrent or metastatic NPC (RM-NPC) refractory to standard 
chemotherapy.
PATIENTS AND METHODS: In this single-arm, multicenter phase II study, patients 
with RM-NPC received 3 mg/kg toripalimab once every 2 weeks via intravenous 
infusion until confirmed disease progression or unacceptable toxicity. The 
primary end point was objective response rate (ORR). The secondary end points 
included safety, duration of response (DOR), progression-free survival (PFS), 
and overall survival (OS).
RESULTS: Among all 190 patients, the ORR was 20.5% with median DOR 12.8 months, 
median PFS 1.9 months, and median OS 17.4 months. Among 92 patients who failed 
at least two lines of systemic chemotherapy, the ORR was 23.9%. The ORRs were 
27.1% and 19.4% in PD-L1+ and PD-L1- patients, respectively (P = .31). Patients 
with ≥ 50% decrease of plasma Epstein-Barr virus (EBV) DNA copy number on day 28 
had significantly better ORR than those with < 50% decrease, 48.3% versus 5.7% 
(P = .0001). Tumor mutational burden had a median value of 0.95 muts/mega-base 
in the cohort and had no predictive value for response. Whole-exome sequencing 
results from 174 patients revealed that the patients with genomic amplification 
in 11q13 region or ETV6 genomic alterations had poor responses to toripalimab.
CONCLUSION: The POLARIS-02 study demonstrated a manageable safety profile and 
durable clinical response of toripalimab in patients with chemorefractory 
metastatic NPC. An early decrease in plasma EBV DNA copy number correlated with 
favorable response.