1. Academic Validation
  2. Novel PD-1 inhibitor prolgolimab: expanding non-resectable/metastatic melanoma therapy choice

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.
Sergey Tjulandin 1 Lev Demidov 1 Vladimir Moiseyenko 2 Svetlana Protsenko 3 Tatiana Semiglazova 3 Svetlana Odintsova 4 Ruslan Zukov 5 Sergey Lazarev 6 Yuliya Makarova 7 Marina Nechaeva 8 Dina Sakaeva 9 Aleksey Andreev 10 Anna Tarasova 11 Natalya Fadeyeva 12 Mariia Shustova 13 Ivan Kuryshev 14
Affiliations

Affiliations

  • 1 N. N. Blokhin National Cancer Research Medical Center of the Ministry of Healthcare of the Russian Federation, Moscow, Russia.
  • 2 Saint Petersburg Clinical Research and Practice Center for Specialized Medical Care (Oncology), Saint Petersburg, Russia.
  • 3 N. N. Petrov National Cancer Research Medical Center, Saint Petersburg, Russia.
  • 4 JSC «Sovremennye Meditsinskie Tekhnologii», Saint Petersburg, Russia.
  • 5 A. I. Kryzhanovsky Krasnoyarsk Regional Clinical Oncology Center, Krasnoyarsk, Russia.
  • 6 Altai Krai Oncology Center, Barnaul, Russia.
  • 7 Clinical Oncology Center No 1 of the Ministry of Healthcare of Krasnodar Krai, Krasnodar, Russia.
  • 8 Arkhangelsk Regional Clinical Oncology Center, Arkhangelsk, Russia.
  • 9 Republican Clinical Oncology Center of the Ministry of Healthcare of the Republic of Bashkortostan, Ufa, Russia.
  • 10 Medical Center of the Federal Medical and Biological Agency, Novosibirsk, Russia.
  • 11 Samara Regional Clinical Oncology Center, Samara, Russia.
  • 12 Chelyabinsk Regional Center of Oncology and Nuclear Medicine, Chelyabinsk, Russia.
  • 13 JSC BIOCAD, Saint Petersburg, Russia. Electronic address: shustova@biocad.ru.
  • 14 JSC BIOCAD, Saint Petersburg, Russia.
Abstract

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 withClinicalTrials.gov(NCT03269565).

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.

Figures
Products