Recombinant humanised anti-PD-1 monoclonal antibody (JS001) treatment for patients with refractory or metastatic nasopharyngeal carcinoma: preliminary results of an open-label, phase 1b/2, clinical study

Abstract Background Patients with unresectable or recurrent nasopharyngeal cancer who have disease progression after standard therapy have few treatment options and represent an important, unmet medical need. Nasopharyngeal cancer is closely associated with Epstein-Barr virus (EBV) infection and has been reported to have high concentrations of PD-L1 expression and tumour-infiltrating lymphocytes, which indicate a potential implication of PD-1 blockade in the treatment of nasopharyngeal cancer. JS001, a humanised recombinant IgG4 antibody against PD-1, selectively blocks the interactions of PD-1, with its ligands PD-L1 and PD-L2, and promotes antigen-specific T-cell activation. Results of a phase 1 study of JS001 treatment in Chinese patients with heavily pretreated solid tumours have shown an acceptable safety profile in doses up to 10 mg/kg once every 2 weeks until progressive disease, intolerance, withdrawal of consent, or investigator decision. Here we report the safety and efficacy of JS001 in a phase 1b/2 clinical study. Methods We did this open-label, phase 1b/2, clinical study in Chinese patients with refractory or metastatic nasopharyngeal cancer received JS001 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity. All patients with measurable disease were assessed for clinical response every 8 weeks according to the immune-related Response Evaluation Criteria In Solid Tumors (iRECIST) criteria. Tumour PD-L1 expression, plasma EBV DNA concentration, and additional potential predictive biomarkers were monitored for correlation with clinical response. This study is registered with ClinicalTrials, number NCT02915432. Findings Between Dec 29, 2016, and June 19, 2017, we enrolled 48 patients with nasopharyngeal cancer. Of 23 evaluable patients, the median age was 46 years (range 33–70), 81% were male, and EBV serology tested positive in 92%. Adverse events occurred in 46 (96%) of 48 patients, which were mostly grade 1 or 2. Grade 3 and worse adverse events occurred in 17 patients (35%), including abnormal liver function (n=6, 13%), dysphagia (n=2, 4%), and pulmonary infection (n=2, 4%). Rapid and deep clinical responses were observed. Seven patients (15%) had partial responses while ten patients (21%) achieved stable disease, with the proportion of patients who achieved an objective response of 30% and a disease control of 73%. The responses seemed unrelated to PD-L1 expression status on tumour biopsy. Interpretation JS001 treatment has shown good clinical activity in heavily pretreated patients with nasopharyngeal cancer and a manageable safety profile. We plan to enrol 54 patients with nasopharyngeal cancer to further monitor the safety and efficacy of JS001 treatment. Funding Shanghai Science and Technology Innovation Fund.