A phase III randomized study comparing BCD-201, a pembrolizumab biosimilar candidate, and reference pembrolizumab in patients with advanced melanoma.

Abstract

9541 Background: The development of clinically comparable biosimilars of key immuno-oncology agents is essential to improving global access to effective therapy. BCD-201 is a proposed pembrolizumab biosimilar that has shown high analytical similarity in preclinical studies, and pharmacokinetic equivalence to the reference pembrolizumab in phase I study (NCT05739006).This phase III trial evaluated the clinical equivalence of BCD-201 versus reference pembrolizumab in patients with advanced melanoma. Methods: This international, multicenter, randomized, double-blind phase III study enrolled adult patients with unresectable or metastatic cutaneous melanoma. Patients were randomized 1:1 to receive BCD-201 or reference pembrolizumab 200 mg IV every 3 weeks for 24 weeks. Randomization was stratified by ECOG (0 vs 1), PD-L1 expression (<5% vs ≥5%), and disease stage (AJCC 7th edition M0/M1a/M1b vs M1c). The primary endpoint was objective response rate (ORR) per RECIST v1.1 assessed by blinded independent central review (BICR) at week 24 in the ITT population. Equivalence was concluded if the 95% confidence interval (CI) for the ORR difference fell within prespecified margins of −15% to +15%. Secondary efficacy endpoints included ORR per iRECIST, progression-free survival (PFS), overall survival (OS). Results: A total of 479 patients were included in the ITT population (BCD-201, n=234; reference pembrolizumab, n=245), with balanced baseline characteristics. At week 24, ORR was 33.3% in the BCD-201 group and 32.7% in the reference pembrolizumab group in ITT population. The unstratified ORR difference was 0.7% (95% CI −7.7 to 9.1), fully within the prespecified equivalence margins. Results were consistent across per-protocol and stratified sensitivity analyses. Secondary efficacy endpoints, including ORR per iRECIST, OS, and DOR, were comparable between groups. At 24 weeks, PFS rates were 51.9% for BCD-201 and 50.5% for reference pembrolizumab per RECIST 1.1. OS rate at 24 week was 90.2% in the BCD-201 group and 89.3% in the reference pembrolizumab group. Longer-term efficacy and safety data will be reported in future analyses. Safety profiles were similar between groups, with grade ≥3 AEs reported in 19.7% and 21.9% of patients for BCD-201 and reference pembrolizumab. Main PK parameters (AUC and C max ) met equivalence criteria. Immunogenicity was low and comparable between groups, with binding antibodies (Abs) detected in 7 (3.1%) and 6 (2.6%) patients in the BCD-201 and comparator groups, respectively. No neutralizing Abs were detected. Conclusions: BCD-201 demonstrated equivalent efficacy to reference pembrolizumab with comparable safety, pharmacokinetics, and immunogenicity in patients with advanced melanoma. These data support BCD-201 as a pembrolizumab biosimilar and highlight its potential to expand access to anti-PD-1 therapy. Clinical trial information: NCT05986331 .