Safety, Tolerability, and Preliminary Efficacy of Serplulimab, a Novel Anti-PD-1 Antibody, in Patients with Metastatic or Recurrent Solid Tumors: A Phase I Study

Background: Serplulimab is a novel, recombinant, humanized, monoclonal, anti-programmed death 1 antibody with a similar or better affinity and pre-clinical antitumor activity than pembrolizumab and nivolumab. Objective: This phase I, open-label, dose-escalation study evaluated serplulimab in patients with advanced solid tumors. The second interim analysis of the dose-finding phase is reported here. Methods: Adult patients with histologically confirmed metastatic/recurrent solid tumors who had progressed on, or were intolerant to/clinically unsuitable for standard treatment, were enrolled. Four intravenous serplulimab dose levels were evaluated: 0.3, 1.0, 3.0, and 10.0 mg/kg every 2 weeks in 28-day cycles for up to 2 years. Primary endpoints were the incidence of treatment-emergent adverse events and the maximum tolerated dose. Results: By 27 July, 2020 (data cut-off), 29 patients with stage IV disease (34.5% with lung cancer) received one or more doses of serplulimab. One (3.4%) patient had completed treatment and 26 (89.7%) had discontinued from the study. The maximum tolerated dose was not reached. Twenty-two (75.9%) patients experienced treatment-emergent adverse events related to serplulimab, most frequently nausea (24.1%), with no notable differences in incidence between dose cohorts; of these, grade ≥ 3 events occurred in four (13.8%) patients. Pharmacokinetic data demonstrated minimal accumulation of serplulimab after repeated administration. Functional programmed death 1 blockade was observed across dose levels. Objective response and disease control rates were 8.0 and 60.0%, respectively. Conclusions: Serplulimab was well tolerated and demonstrated antitumor activity. These data support further study of serplulimab in larger patient populations. Clinical Trial Registration: ClinicalTrials.gov NCT03468751 (19 March, 2018).