Recombinant Humanized Anti-Pd-1 Monoclonal Antibody (JS001) in Patients with Refractory/metastatic Nasopharyngeal Carcinoma: Preliminary Results of an Open-Label Phase II Clinical Study

Background: Patients with metastatic nasopharyngeal cancer (NPC) who experienced disease progression after standard therapy have limited treatment options. NPC is closely associated with Epstein–Barr Virus (EBV) infection and has been reported to have high levels of PD-L1 expression and tumor infiltrating lymphocytes, favoring immune-therapy potential in treating NPC. JS001, a humanized 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. Phase I studies of JS001 in subjects with heavily pretreated solid tumors had demonstrated an acceptable safety profile in doses up to 10 mg/kg Q2W. Methods: Refractory/metastatic NPC Patients received JS001 3 mg/kg Q2W until disease progression or unacceptable toxicity. All patients with measurable disease were assessed for clinical response every 8 weeks. Tumor PD-L1 expression (SP142) and plasma EBV DNA levelwere monitored for correlation with clinical response. Results: Between Dec 22th 2016 and May 4th 2018, 139 NPC pts were enrolled into the study. The median age was 46 years, 84% male (n = 117), with average 3.4 lines of prior systemic therapies. By Nov 15th 2017, treatment related AEs occurred in 84% patients, which were mostly grade 1 or 2, including fever (18.2%), hypothyroidism (18.2%), proteinuria (10.9%), fatigue (9.1%), TBIL increase (9.1%), leukopenia (9.1%) and anemia (7.3%). Grade ≥ 3 treatment related AEs occurred in 14.5% patients. Out of 52 evaluable pts by Jan 2018, 16 partial responses (30.8% ORR) and 16 stable diseases (61.5% DCR) were observed. PD-L1+ pts had slightly higher ORR 38.5% and 65.4% DCR. Interestingly, an average drop of 47-fold plasma EBV DNA copy number was observed in responding pts, which typically proceeded the radiographic identification of clinical benefits. Conclusions: PD-1 mAb JS001 has demonstrated encouraging clinical activity in heavily pretreated NPC pts and a manageable safety profile. A change in plasma EBV DNA copy number might serve as a prognosis marker for NPC upon immunotherapy. Clinical trial identification: NCT02915432. Legal entity responsible for the study: Shanghai Junshi Biosciences Co. Funding: Shanghai Junshi Biosciences Co. Disclosure: H. Wu, H. Feng, S. Yao: Employee: Shanghai Junshi Biosciences Co. All other authors have declared no conflicts of interest.