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

Eur J Cancer. 2021 May:149:222-232. doi: 10.1016/j.ejca.2021.02.030. Epub 2021 Apr 17.


Background: 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.

Methods: 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

Results: 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.

Conclusions: 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.

Keywords: Anti–PD-1; Immunotherapy; Melanoma; Prolgolimab.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Disease Progression
  • Drug Administration Schedule
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage*
  • Immune Checkpoint Inhibitors / adverse effects
  • Male
  • Melanoma / drug therapy*
  • Melanoma / immunology
  • Melanoma / mortality
  • Melanoma / pathology
  • Middle Aged
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / immunology
  • Progression-Free Survival
  • Russia
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Time Factors


  • Immune Checkpoint Inhibitors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor

Associated data