Results of phase III clinical trial of novel biosimilar of pembrolizumab (RPH-075).

9558 Background: Pembrolizumab is a high-affinity humanized antibody to the PD-1 receptor. This study investigated the efficacy and safety profile of RPH-075, a biosimilar of original pembrolizumab, in patients with advanced skin melanoma. Methods: CL01860211 was an international, multicenter, double-blind, randomized, phase III comparative study. The study was based on the following hypothesis: RPH-075 is non-inferior to pembrolizumab (Keytruda) in objective response rate (ORR) at 24 weeks from the start of therapy in patients with unresectable or metastatic melanoma as 1 st or 2 nd line therapy, not previously treated with pembrolizumab or other anti-PD-1/PD-L1/PD-L2 agents. Pembrolizumab was administered intravenously at a dose of 200 mg Q3W until progression or intolerable toxicity (but no longer than 2 years). ORR was assessed in the per protocol (РР) population according to RECIST 1.1 and iRECIST criteria by an Independent Radiology Review Committee. Disease control rate (DCR), progression-free survival (PFS), were the secondary endpoints. Safety assessment was carried out throughout the study. Adverse events (AE) were assessed by CTCAE v5.0. Immunogenicity was also evaluated over 24 weeks of therapy. Results: A total of 266 patients were randomized in 2 groups (n=137 in RPH-075 group and n=129 in pembrolizumab group). The median age was 66 years (range 27–87). The majority of patients had ECOG 0-1 – 96.24%. Most of the patients (90.60%) received pembrolizumab as 1st line treatment. Metastases in the CNS were identified in 10.53% patients. ORR was 28.35% [95% CI: 21.23; 36.73] in RPH-075 group and 24.56% [95% confidential interval (CI): 17.57; 33.21] in pembrolizumab group (p = 0.604). The relative risk was 1.154 [95% CI: 0.755; 1.764]. The lower margin of the obtained 95% CI is higher than the lower margin (0.664) established in the hypothesis. DCR was 48.03% in RPH-075 group and 35.09% in pembrolizumab group (p = 0.057). Median PFS was 3.02 months in RPH-075 group and 2.76 in pembrolizumab group (p = 0.058). Treatment-related adverse events of any grade were registered for 39.13% of patients in RPH-075 group and for 43.75% of patients in pembrolizumab group (p = 0.457). During the main period, anti-drug antibodies (ADA) were detected in 6 patients: 3 (2.36%) in the RPH-075 group and 3 (2.46%) in the pembrolizumab group. None of the patients with detected ADA had neutralizing activity of antibodies to pembrolizumab and no imAEs were registered. Conclusions: The non-inferior efficacy of RPH-075 relative to pembrolizumab had been confirmed along with similar safety profile. Clinical trial information: NCT06320353 .