Novel PD-1 inhibitor prolgolimab: expanding non-resectable/metastatic melanoma therapy choice

• Published in: European journal of cancer (1990) 2021-05, Vol.149, p.222-232
• Main Authors: Tjulandin, Sergey, Demidov, Lev, Moiseyenko, Vladimir, Protsenko, Svetlana, Semiglazova, Tatiana, Odintsova, Svetlana, Zukov, Ruslan, Lazarev, Sergey, Makarova, Yuliya, Nechaeva, Marina, Sakaeva, Dina, Andreev, Aleksey, Tarasova, Anna, Fadeyeva, Natalya, Shustova, Mariia, Kuryshev, Ivan
• Format: Article
• Language: English
• Subjects: Adverse events; Anticancer properties; Anti–PD-1; Apoptosis; Autoimmune diseases; Cell death; CTLA-4 protein; Cytotoxicity; Dosage; Immunoglobulin G; Immunotherapy; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Lymphocytes; Lymphocytes T; Melanoma; Metastases; Monoclonal antibodies; Mutation; PD-1 protein; Prolgolimab; Proteins; Response rates; Safety management; Solid tumors; Subgroups; Survival; Therapy; Toxic diseases; Toxicity; Tumors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2021.02.030

Prolgolimab is an IgG1 anti–PD-1 (programmed cell death protein 1) monoclonal antibody containing the Fc-silencing ‘LALA’ mutation. We assessed the efficacy and safety of two dosing regimens of prolgolimab in patients with advanced melanoma in a multicenter open-label parallel-arm phase II trial (MIRACULUM). We present the final analysis after 1 year of follow-up and additional efficacy results from 2 years of follow-up. Patients with advanced cutaneous or non-cutaneous melanoma, including stable brain metastasis, without autoimmune disease and who underwent no prior targeted therapy, anti–PD-(L)1 or anti–CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) therapy were randomly assigned (1:1) to receive prolgolimab in 2 dosing regimens, 1 mg/kg every 2 weeks (arm 1) or 3 mg/kg every 3 weeks (arm 2), until disease progression or intolerable toxicity. Randomisation was stratified based on performance status (Eastern Cooperative Oncology Group 0 or 1), lactate dehydrogenase levels (elevated or normal) and prior systemic therapy (naive or previously treated). The primary outcome was the objective response rate, assessed as per immune-related Response Evaluation Criteria in Solid Tumours by independent central review. The hypothesis that each dosing regimen of prolgolimab has an overall response rate >28% was tested independently for each study arm comprising all patients who received at least one dose of prolgolimab. Exploratory assessment of efficacy, including subgroup analysis, at 2 years of follow-up was not specified in the protocol. This study is registered withClinicalTrials.gov(NCT03269565). Between August 2017 and March 2018, 126 patients with advanced melanoma were enrolled. At main 1-year data cut-off, the median follow-up was 13.8 and 14.5 months in arm 1 and 2, respectively. An objective response was observed in 38.1% of patients (arm 1) and in 28.6% (arm 2). Grade III–IV treatment-related adverse events occurred in 12.7% and 3.2% of patients in arm 1 and 2, respectively. For exploratory efficacy analysis, the median follow-up was 25.4 and 25.7 months in arm 1 and 2, respectively. The 2-year progression-free survival was 33.3% in arm 1 and 30.2% in arm 2, and the 2-year overall survival was 57.1% and 46.0%, respectively. The MIRACULUM study met its primary end-point in both the study arms. Prolgolimab showed significant antitumour activity and a manageable safety profile in patients with advanced melanoma. •The article describes the phase II tria