A phase 1 study of fixed-dose regimens of serplulimab, an anti-PD-1 antibody, in patients with advanced solid tumors.

Abstract

2596 Background: Serplulimab is a recombinant humanized IgG4 monoclonal antibody targeting PD-1. A two-cohort phase 1 study was conducted to evaluate the safety of serplulimab monotherapy in patients with advanced solid tumors (NCT03468751). Findings from the dose-finding cohort has been previously reported at the 2022 ASCO Annual Meeting (No. e14560). Here we present results from the dose expansion cohort, in which fixed-dose regimens were evaluated. Methods: This multicenter phase 1 study enrolled patients with locally advanced or metastatic solid tumors who have failed or are intolerant to standard therapy or for whom no standard therapy is available. In the dose expansion cohort, patients received intravenous serplulimab at 200 mg Q2W, 300 mg Q3W, 400 mg Q4W, or 600 mg Q6W. The primary endpoints were adverse event profile and maximum tolerated dose (MTD). Secondary endpoints included pharmacokinetic (PK), immunogenicity, pharmacodynamics (PD), and efficacy. Results: As of data cut-off on Jan 5, 2024, 37 patients received at least one dose of serplulimab at 200 mg Q2W (n = 9), 300 mg Q3W (n = 9), 400 mg Q4W (n = 10), or 600 mg Q6W (n = 9). All patients were Asian, 70.3% male; median age was 60.0 yrs (range 33–88). Patients had head and neck cancer (n = 10, 27.0%), esophageal cancer (n = 6, 16.2%), colorectal cancer (n = 4, 10.8%) or other types of tumor. Most patients had metastatic disease (64.9%). All patients had prior systemic cancer treatment, including 4 (10.8%) with prior immunotherapy; 51.4% had ≥ 3 prior lines of therapy. All 37 patients were included in safety, PK, and PD analyses; 35 response-evaluable patients were included in efficacy analysis. No dose-limiting toxicity was reported, and MTD has not been determined. Treatment-related adverse events (TRAEs) were observed in 19 patients (51.4%), including 7 (18.9%) reporting grade ≥ 3 TRAE. TRAE incidence was similar across regimen groups. Following multiple infusions, the geometric mean t ½, ss was from 341.1–751.3 h, and geometric mean CL ss was 0.006–0.009 L/h. Treatment-emergent anti-drug antibody (ADA) was detected in 7 (18.9%) patients. No difference in safety or PK was noted between ADA-positive and -negative patients. Profiles of PD-1 receptor occupancy in circulating CD3 + T cells and interleukin-2 stimulation ratio were similar across dose groups, suggesting dose-independent functional blockade. Six patients (300 mg Q3W, 4; 400 mg Q4W, 2) achieved partial response, resulting in an ORR of 17.1%. Among the responders, 12-month duration of response rate was 66.7% (95% CI confidence interval, 19.5–90.4). Median progression-free survival was 2.3 months (95% CI, 1.9–5.1). Conclusions: Fixed-dose regimens of serplulimab showed favorable safety, PK, and PD characteristics and preliminary anti-tumor activity, supporting its further investigation. Clinical trial information: NCT03468751 .