A phase 1 study of serplulimab, a novel humanized monoclonal anti-PD-1 antibody, in patients with advanced solid tumors.

Abstract

e14560 Background: Serplulimab, a novel humanized IgG4 monoclonal antibody against PD-1 receptor, increased functional activities of human T cells and showed anti-tumor activity in several xenograft models. This phase 1 study was designed to assess the safety and tolerability of serplulimab in patients with metastatic or recurrent solid tumors. Methods: This prospective, open-label, two-cohort (dose-finding cohort [up to 30 patients]; dose expansion cohort [up to 27 patients]) phase 1 study was conducted in patients with metastatic or recurrent solid tumors who had failed standard therapy. In the dose-finding cohort, Bayesian optimal interval (BOIN) design was adopted to explore the MTD of serplulimab. Patients were administered serplulimab (Q2W) at doses of 0.3, 1, 3, or 10 mg/kg via intravenous infusion until disease progression, the maximum of 1 year, withdrawal from the study, or death, whichever occurred first. In the dose expansion cohort, nine eligible patients were enrolled in each dose group to receive fixed doses of serplulimab at 200 (Q2W), 300 (Q3W) or 400 mg (Q4W). The primary objective of this study was to identify the safety profile and the MTD of serplulimab. The PK profile and the preliminary efficacy were also examined as secondary objectives. Results: Here we only report the results from the dose-finding cohort. As of July 27, 2020, 29 patients were enrolled and treated with at least one dose of serplulimab (0.3 mg/kg group, n = 3; 1 mg/kg group, n = 4; 3 mg/kg group, n = 6; 10 mg/kg group, n = 16). At baseline, the mean age of enrolled patients was 60.0 years, with a mean BMI of 24.7 kg/m2, a mean BSA of 1.7 m2, and a mean LVEF of 67.1%. All patients presented with stage IV tumors at baseline, among whom 79.3% were diagnosed with metastatic disease. Only one patient in the 3 mg/kg dose group experienced DLTs, which was reported during the first cycle. The MTD was not determined yet. Overall, 28 (96.6%) patients experienced at least one TEAE during the study, mostly of grade 1 or 2. No notable differences were observed among the dose groups with regard to the incidence of TEAEs. The most frequently reported TEAEs was decreased appetite (41.4%), fatigue (31.0%), nausea (27.6%), pyrexia (27.6%), and pleural effusion (27.6%). Minimal accumulation of serplulimab was observed following multiple dose administrations. The preliminary anti-tumor efficacy of serplulimab was demonstrated by a DCR of 60.0%, an ORR of 8.0%, and a median PFS of 107.0 days. Conclusions: In summary, serplulimab up to 10 mg/kg was well tolerated and showed promising anti-tumor activity in patients with metastatic or recurrent solid tumors. Serplulimab is currently being investigated in phase 3 studies among patients with NSCLC, SCLC, esophageal cancer, mCRC, etc. Clinical trial information: NCT03468751.