Improved clinical outcomes with low-dose anti-CTLA-4 (Nurulimab) plus anti-PD-1 (Prolgolimab) vs. anti-PD-1 monotherapy in advanced cutaneous melanoma: Results from the phase III OCTAVA trial

  • Eur J Cancer. 2025 Sep 9:227:115674. doi: 10.1016/j.ejca.2025.115674.
Lev Demidov  1 ,  Igor Samoylenko  1 ,  Galina Kharkevich  1 ,  Kristina Orlova  1 ,  Vladimir Moiseenko  2 ,  Igor Utyashev  3 ,  Daniil Stroyakovskiy  4 ,  Vadim Kozlov  5 ,  Anastasia Zimina  6 ,  Anastasia Mochalova  7 ,  Svetlana Demidova  8 ,  Marina Lyadova  9 ,  Andrey Kutkovich  10 ,  Pavel Skopin  11 ,  Nadezhda Kovalenko  12 ,  Sufia Safina  13 ,  Vitaliy Volkov  14 ,  Yulia Semiletova  15 ,  Vera Vaschenko  16 ,  Nikolay Kislov  17 ,  Artem Poltoratskiy  18 ,  Irina Shumskaya  19 ,  Sergey Kolomiets  20 ,  Alexandr Sobolev  21 ,  Igor Belogortsev  22 ,  Svetlana Odintsova  23 ,  Sameer Rastogi  24 ,  Timur Andabekov  25 ,  Konstantin Penkov  26 ,  Anna Semenova  27 ,  Alexey Obukhov  28 ,  Vasiliy Belyakovsky  29 ,  Alexander Yurchenkov  4 ,  Oleg Gladkov  30 ,  Rakesh Neve  31 ,  Natalia Falaleeva  32 ,  Elena Poddubskaya  33 ,  Amale Vaibhav  34 ,  Dmitriy Kirtbaya  35 ,  Yana Chapko  36 ,  Maria Smagina  37 ,  Natalya Fadeeva  38 ,  Irina Sorokina  39 ,  Evgenia Mikhailova  40 ,  Yulia Linkova  40 ,  Arina Zinkina-Orikhan  40 ,  Anton Lutskii  40 ,  Rishat Gabidullin  40 ,  Roman Rzaev  40 ,  Fedor Kryukov  40
Affiliations
  • 1. FSBI "N.N. Blokhin National Medical Research Center for Oncology", MoH, Moscow, Russian Federation.
  • 2. SBHI "N.P. Napalkov St. Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)", St. Petersburg, Russian Federation.
  • 3. Hadassah Medical LCC, Moscow, Russian Federation.
  • 4. Moscow City Oncology Hospital No. 62, Moscow, Russian Federation.
  • 5. SBHI "Novosibirsk Regional Clinical Oncology Dispensary", Novosibirsk, Russian Federation.
  • 6. BHI "Clinical Oncology Dispensary", Omsk, Russian Federation.
  • 7. JSC Medsi Group of Companies, Moscow, Russian Federation.
  • 8. Health care institution "Minsk City Clinical Oncology Center", Minsk, Belarus.
  • 9. SBHI "City Clinical Oncology Hospital No. 1 of the Moscow City Health Department", Moscow, Russian Federation.
  • 10. LLC Stepmed Clinic, Moscow, Russian Federation.
  • 11. FSBEI of Higher Education "National Research Mordovian State University named after N.P. Ogarev", Saransk, Russian Federation.
  • 12. SBHI Volgograd Regional Clinical Oncology Dispensary, Volgograd, Russian Federation.
  • 13. SAHI "Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of Tatarstan named after Professor M. Z. Sigal", Kazan, Russian Federation.
  • 14. Healthcare Institution "Brest Regional Oncology Dispensary", Brest, Belarus.
  • 15. FSBEI of Higher Education "Saint Petersburg State University", St. Petersburg, Russian Federation.
  • 16. RSBHI "Kostroma Oncology Dispensary", Kostroma, Russian Federation.
  • 17. SBHI "Regional Clinical Oncology Hospital", Yaroslavl, Russian Federation.
  • 18. FSBI "N.N. Petrov National Medical Research Center for Oncology", MoH, St. Petersburg, Russian Federation.
  • 19. SBHI "Nizhny Novgorod Regional Clinical Oncology Dispensary", Nizhny Novgorod, Russian Federation.
  • 20. RSBHI "Altai Regional Oncology Dispensary", Barnaul, Russian Federation.
  • 21. SBHI "Kuzbass clinical oncological dispensary named after M.S. Rappoport", Novokuznetsk, Russian Federation.
  • 22. SBHI «Leningrad Regional Clinical Hospital», St. Petersburg, Russian Federation.
  • 23. JSC Modern Medical Technologies, St. Petersburg, Russian Federation.
  • 24. All India Institute Of Medical Sciences Delhi, New Delhi, India.
  • 25. Limited Liability Company AV Medical Group, St. Petersburg, Russian Federation.
  • 26. Private Medical Institution "Euromedservice", St. Petersburg, Russian Federation.
  • 27. FSBI "National Medical Research Center of Oncology named after N.N. Petrov" of the Ministry of Health of the Russian Federation, St. Petersburg, Russian Federation.
  • 28. SHI "Vitebsk Regional Clinical Oncology Dispensary", Vitebsk, Belarus.
  • 29. HI "Gomel Regional Clinical Oncology Dispensary", Gomel, Belarus.
  • 30. Limited Liability Company EVIMED, Chelyabinsk, Russian Federation.
  • 31. PDEAS Ayurved Rugnalaya & Steriling Multispeciality Hospital, Pimpri-Chinchwad, India.
  • 32. FSBI "National Medical Research Center of Radiology" of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation.
  • 33. FSAEI of Higher Education I.M. Sechenov First Moscow Medical University, MoH, Moscow, Russian Federation.
  • 34. Horizon Multispecialty Hospital, Sangli Miraj Kupwad, India.
  • 35. SBHI "Oncology Dispensary No. 2", MoH of the Krasnodar Territory, Sochi, Russian Federation.
  • 36. State Budgetary Healthcare Institution of the Arkhangelsk Region "Arkhangelsk Clinical Oncology Dispensary", Arkhangelsk, Russian Federation.
  • 37. State Budgetary Healthcare Institution Leningrad Regional Clinical Hospital, St. Petersburg, Russian Federation.
  • 38. SBHI "Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine", Chelyabinsk, Russian Federation.
  • 39. MCSC named after A.S.Loginov, Russian Federation; JSC Biocad, Russian Federation. Electronic address: [email protected].
  • 40. JSC Biocad, Russian Federation.
PMID: 40795521 DOI: 10.1016/j.ejca.2025.115674
Abstract

Background: OCTAVA (NCT05732805) was an international, multi-center, randomized, double-blind, phase III study evaluating the fixed-dose combination of nurulimab (anti-CTLA-4) and prolgolimab (anti-PD-1) (BCD-217, Nuru+Prolgo) followed by prolgolimab maintenance versus prolgolimab monotherapy as first-line treatment for unresectable or metastatic melanoma (un/mM). We present the primary analysis results.

Methods: Treatment-naïve patients with un/mM were randomized 1:1 to Nuru+Prolgo (n = 135) or prolgolimab (n = 136) for 4 cycles, followed by prolgolimab maintenance for up to two years. The primary endpoint was progression-free survival (PFS) by iRECIST.

Results: With a median follow-up of 15.8 months, median PFS was significantly longer with nurulimab+prolgolimab [15.4 months (95 % CI, 10.3-ND)] compared to prolgolimab monotherapy [10.8 months (4.7-ND)] (HR 0.68; 95 % CI, 0.482-0.957; iRECIST). RECIST 1.1 analysis confirmed this benefit (mPFS 9.9 vs 2.8 months). ORR and DCR were also higher in the combination arm. Grade 3-4 treatment-related AE: 16.3 % (combination) vs 14.0 % (monotherapy). Immune-related AEs (irAE): 52.6 % vs 32.4 % (p = 0.0007); Gr. ≥ 3 irAE: 13.3 % vs 5.9 % (p = 0.04). Discontinuations due to AE: 9.6 % vs 4.4 %.

Conclusions: The Nuru+Prolgo fixed-dose combination demonstrated significantly superior efficacy versus aPD-1 monotherapy in first-line un/mM, with a manageable safety profile.

Keywords
Anti-CTLA-4; Anti-PD-1; Nurulimab; Prolgolimab; Unresectable and metastatic melanoma.
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