The first domestic combination of nurulimab + prolgolimab: from clinical development and economic analysis to real-world use in disseminated melanoma

Immunotherapy with immune checkpoint inhibitors has dramatically shifted the prognosis for outcomes of melanoma treatment. However, enhancing the efficacy of dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 while reducing immune-mediated toxicity remains a clinically significant challenge. This article presents a systematic review of data on the first homegrown fixed-dose combination of dual immune checkpoint inhibitors: anti-CTLA-4 + anti-PD-1 (Nurulimab) + Prolgolimab (Nurdati, BCD-217). We searched articles in the PubMed/MEDLINE, eLIBRARY, ClinicalTrials.gov, Cochrane Library databases, and specialized oncology congress records, using the following keywords in different combinations: unresectable/metastatic melanoma, immunotherapy, checkpoint inhibitors, nurulimab, prolgolimab, Nurdati. A total of 146 articles and information sources were identified at the first stage. After removing duplicates and materials irrelevant to the review topic 118 records were selected for screening, of which 54 were included in the qualitative analysis. The final review included articles and records covering the molecular and pharmacological properties of nurulimab and prolgolimab, the results of the BCD-217 clinical development, comparative efficacy and safety data, and a cost-effectiveness analysis. The excluded articles got the following reasons in favour of exclusion: inappropriateness, lack of clinical data, duplicate results, and limited access to the full text. In the randomized phase III OCTAVA study, the combination of nurulimab plus prolgolimab demonstrated significantly superior efficacy over prolgolimab monotherapy in terms of median progression-free survival (PFS) with comparable cumulative incidence rates of grade 3–4 AEs. Nurdati is a homegrown innovative medicine that is based on a low-dose CTLA-4 blockade and standard anti-PD-1 therapy, demonstrating durable disease control in a patient with BRAF-wild-type acral melanoma in the presented clinical case.

1. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373(1):23–34. https://doi.org/10.1056/nejmoa1504030.

2. Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL et al. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2017;377(14):1345–1356. https://doi.org/10.1056/NEJMoa1709684.

3. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD et al. Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2019;381(16):1535–1546. https://doi.org/10.1056/NEJMoa1910836.

4. Lebbé C, Meyer N, Mortier L, Marquez-Rodas I, Robert C, Rutkowski P et al. Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial. J Clin Oncol. 2019;37(11):867–875. https://doi.org/10.1200/JCO.18.01998.

5. Willsmore ZN, Coumbe BGT, Crescioli S, Reci S, Gupta A, Harris RJ et al. Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: Treatment of melanoma and immune mechanisms of action. Eur J Immunol. 2021;51(3):544–556. https://doi.org/10.1002/eji.202048747.

6. Kryukov F, Semiglazova T, Moiseenko V, Orlova K, Odintsova S, Saygusheva M et al. A phase I dose escalation trial of BCD-145 in patients with unresectable or metastatic melanoma. J Clin Oncol. 2024;42(16 Suppl.):9526. https://doi.org/10.1200/JCO.2024.42.16_suppl.9526.

7. Gordeev A, Vaal A, Puchkova M, Smirnova I, Doronin A, Znobishcheva A et al. Preclinical comparison of prolgolimab, pembrolizumab and nivolumab. Sci Rep. 2024;14(1):23136. https://doi.org/10.1038/s41598-024-72118-3.

8. Tjulandin S, Demidov L, Moiseyenko V, Protsenko S, Semiglazova T, Odintsova S et al. Novel PD-1 inhibitor prolgolimab: expanding non-resectable/metastatic melanoma therapy choice. Eur J Cancer. 2021;149:222–232. https://doi.org/10.1016/j.ejca.2021.02.030.

9. Demidov L, Kharkevich G, Petenko N, Moiseenko V, Protsenko S, Semiglazova T et al. A phase III study to access the safety and efficacy of prolgolimab 250 mg fixed dose administered every 3 weeks versus prolgolimab 1 mg/kg every 2 weeks in patients with metastatic melanoma (FLAT). Front Oncol. 2024;14:1385685. https://doi.org/10.3389/fonc.2024.1385685.

10. Samoylenko IV, Demidov LV, Moiseenko FV, Dvorkin MV, Demidova SA, Protsenko SA et al. Efficacy and safety of nurulimab+prolgolimab with continued prolgolimab therapy compared to prolgolimab alone as first-line therapy in patients with unresectable or metastatic melanoma: final results of the phase II OBERTON clinical study. Journal of Modern Oncology. 2023;25(3):313–324. (In Russ.) https://doi.org/10.26442/18151434.2023.3.202463.

11. Demidov L, Samoylenko I, Kharkevich G, Orlova K, Moiseenko V, Utyashev I et al. 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;227:115674. https://doi.org/10.1016/j.ejca.2025.115674.

12. Demidov L, Samoylenko I, Kharkevich G, Orlova K, Moiseenko V, Utyashev I et al. Proved clinical benefit of low-dose anti-CTLA4 + anti-PD-1 immunotherapy versus mono anti-PD-1 therapy in patients unresectable or metastatic melanoma: phase III OCTAVA trial. Cancer Res. 2025;85(8 Suppl. 1):653. https://doi.org/10.1158/1538-7445.AM2025-653.

13. Fedenko AA, Sedova MV, Kolomeytseva AA, Batov MA, Mironenko ON, Sapozhnikov KV et al. Comparative efficacy and safety of prolgolimab + nurulimab and nivolumab + ipilimumab in the first-line therapy of metastatic or unresectable melanoma: A systematic review and matching-adjusted indirect comparison. Journal of Modern Oncology. 2025;27(3):225–245. (In Russ.) https://doi.org/10.26442/18151434.2025.3.203473.

14. Самойленко ИВ, Банов СМ, Белышева ТС, Демидов ЛВ, Зарецкий АР, Зиновьев ГВ и др. Меланома кожи и слизистых оболочек: клинические рекомендации. М.; 2025. 135 с. Режим доступа: https://cr.minzdrav.gov.ru/preview-cr/921_1.

15. Zyryanov SK, Zhukova NV. Cost-effectiveness analysis of nurulimab and prolgolimab combination used in adult patients with unresectable or metastatic cutaneous melanoma. Farmakoekonomika. Modern Pharmacoeconomics and Pharmacoepidemiology. 2025;18(4):453–464. (In Russ.) https://doi.org/10.17749/2070-4909/farmakoekonomika.2025.320.

16. Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz LH, Mandrekar S et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017;18(3):e143–e152. https://doi.org/10.1016/S1470-2045(17)30074-8.

17. Mulkey F, Theoret MR, Keegan P, Pazdur R, Sridhara R. Comparison of iRECIST versus RECIST V.1.1 in patients treated with an anti-PD-1 or PD-L1 antibody: pooled FDA analysis. J Immunother Cancer. 2020;8(1):e000146. https://doi.org/10.1136/jitc-2019-000146.

18. Muto Y, Fujimura T, Asano Y. Recent Advances in Immunotherapy for Melanoma: Perspectives on the Development of Novel Treatments: A Mini Review. Cancers (Basel). 2025;17(13):2265. https://doi.org/10.3390/cancers17132265.

19. Swetter SM, Johnson D, Albertini MR, Barker CA, Bateni S, Baumgartner J et al. NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2024. J Natl Compr Canc Netw. 2024;22(5):290–298. https://doi.org/10.6004/jnccn.2024.0036.

20. Anokhina Y, Rubinchik V, Yaremenko Y, Teletaeva G, Latipova D, Semenova A et al. Ipilimumab in patients with disseminated melanoma: the N.N. Petrov National Medical Research Center of Oncology expanded access program experience. Voprosy Onkologii. 2018;64(3):388–393. (In Russ.) https://doi.org/10.37469/0507-3758-2018-64-3-388-393.

21. Curti BD, Faries MB. Recent Advances in the Treatment of Melanoma. N Engl J Med. 2021;384(23):2229–2240. https://doi.org/10.1056/NEJMra2034861.

22. Protsenko SA, Imyanitov EN, Semenova AI, Latipova DK, Novik AV, Yurlov DO, Oganesian AP. Modern combined targeted and immunotherapy of metastatic skin melanoma. Meditsinskiy Sovet. 2020;(20):54–61. (In Russ.) https://doi.org/10.21518/2079-701X-2020-20-54-61.

23. Boutros A, Tanda ET, Croce E, Catalano F, Ceppi M, Bruzzone M et al. Activity and safety of first-line treatments for advanced melanoma: A network meta-analysis. Eur J Cancer. 2023;188:64–79. https://doi.org/10.1016/j.ejca.2023.04.010.

24. Robert C, Grob JJ, Stroyakovskiy D, Karaszewska B, Hauschild A, Levchenko E et al. Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma. N Engl J Med. 2019;381(7):626–636. https://doi.org/10.1056/NEJMoa1904059.

25. Knight A, Karapetyan L, Kirkwood JM. Immunotherapy in Melanoma: Recent Advances and Future Directions. Cancers (Basel). 2023;15(4):1106. https://doi.org/10.3390/cancers15041106