Final Results of Phase II Trial (MIRACULUM) of the Novel PD-1 Inhibitor Prolgolimab in Patients with Advanced Melanoma

Tjulandin, Sergei; Fedyanin, Mikhail; Демидов, Лев В.; Moiseyenko, V.; Проценко, Светлана; Odintsova, Svetlana; Semiglazova, Tatiana; Zukov, Ruslan; Lazarev, Sergey; Andreev, Aleksey; Nechaeva, M.; Makarova, J. A.; Fadeeva, Natalia; Tarasova, Anna; Kozlova, O.; Shustova, M.; Гарипов, А. С.; Ivanov, Roman

doi:10.1093/annonc/mdz451.027

Cited by 4 publications

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“…Наблюдаемые расхождения, по-видимому, могут быть обусловлены тем, что период активного проведения КИ OBERTON пришелся на пиковые месяцы заболеваемости новой коронавирусной инфекцией (COVID-19). Это привело к достаточно высокой доле пациентов с НЯ, связанными с COVID-19, в том числе с НЯ, отвечающими критериям серьезности, НЯ с летальным исходом (2 случая) или потребовавшими длительной отмены терапии [31,32]. Так, частота пневмоний на фоне развития COVID-19 3-5-й степени тяжести встречалась ≈10 раз чаще в группе терапии пролголимаба по сравнению с группой терапии нурулимаб+пролголимаб -6 (10,2%) и 1 (1,7%) соответственно.…”

Section: Discussionunclassified

“…Таким образом, по результатам проведенного исследования II фазы показано преимущество КИТ нурулимаб+пролголимаб с переходом на пролголимаб над пролголимабом в монорежиме в отношении ВБП, ЧОО и ЧКЗ при благоприятном профиле безопасности, что в целом согласуется с ранее полученными данными как для пролголимаба, так и для других препаратов из класса блокаторов CTLA-4 и PD-1 [31,32].…”

Section: Discussionunclassified

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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

Samoylenko,

Demidov,

Moiseenko

et al. 2023

J. Mod. Onco.

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Background. In an era of breakthroughs in cancer immunotherapy, CheckMate 067 studies declared the combination of PD-1 and CTLA-4 inhibitors a new standard of care for patients with metastatic melanoma (MM). A significant limitation of the widespread use of the combination of ipilimumab and nivolumab in routine clinical practice is the high risk of severe immune-mediated adverse events. Prolgolimab and nurulimab are a combination of fixed doses of original monoclonal antibodies (manufactured by JSC "BIOCAD," Russia) to the PD-1 receptor (prolgolimab) and the CTLA-4 receptor (nurulimab) (3:1 ratio). This paper presents the results of an international, multicenter, double-blind, placebo-controlled, comparative, randomized, phase II OBERTON clinical study to investigate the efficacy and safety of nurulimab + prolgolimab combination therapy with continued prolgolimab therapy compared to prolgolimab alone as first-line therapy in patients with unresectable melanoma (uRM) or MM (NCT03913923). Materials and methods. The study included patients with uRM or MM who were not previously treated for metastatic disease. The patients were randomized into two groups (1:1). Patients in group 1 were treated with a nurulimab (1 mg/kg) and prolgolimab (3 mg/kg) combination at a dose of 0.2 mL/kg (equivalent to 1 mg/kg of nurulimab and 3 mg/kg of prolgolimab) once every 3 weeks during the first 4 blinded infusions. Patients in group 2 received prolgolimab monotherapy at a dose of 3 mg/kg once every 3 weeks during the first 4 blinded infusions. Starting from infusion 5, patients in both groups received open prolgolimab 1 mg/kg once every 2 weeks. The primary endpoint of the study was progression-free survival (PFS). The study is registered on ClinicalTrials.gov under the number NCT05732805 and is currently ongoing, but recruitment of new patients has been completed. Results. One hundred seventeen patients were randomized and received at least one dose of the study therapy. At a median follow-up of 16.79 months, the median PFS was 12.2 (4.9; not achieved) months in the nurulimab + prolgolimab group and 2.8 (1.5; 4.7) months in the prolgolimab monotherapy group (95% confidence interval 0.36-0.90, hazard ratio 0.57). PFS at 24 months was 41% in the nurulimab + prolgolimab group and 25.4% in the prolgolimab monotherapy group. In both groups, the therapy was well tolerated. Grade 3-4 immune-mediated adverse events were reported in 15.5% of patients who received nurulimab + prolgolimab, compared with 1.7% of those who received prolgolimab alone. The most frequent grade 3-4 treatment-related adverse events in both treatment groups were increased alanine aminotransferase and aspartate aminotransferase and asthenia. Overall, the safety profile was favorable, as expected for the class of immune checkpoint inhibitors, anti-CTLA-4, and anti-PD-1 monoclonal antibodies. Discussion. The results demonstrate a favorable safety profile in both the nurulimab + prolgolimab combination and prolgolimab monotherapy groups as the first-line treatment for uRM or MM. The assessment of the primary endpoint, PFS, showed the benefit of combination immunotherapy followed by switching to prolgolimab compared to prolgolimab alone. Conclusion. Combination immunotherapy with the CTLA-4 inhibitor nurulimab and the PD-1 inhibitor prolgolimab, available as a combination of solutions of two drugs in a single vial, with a further switch to monotherapy with prolgolimab, can fill an important niche in the treatment of patients with uRM or MM. Confirmation of the obtained data on the efficacy and safety of the combined regimen of nurulimab + prolgolimab in comparison with PD-1 inhibitor monotherapy is expected from the ongoing phase III BCD-217-2 OCTAVA study (NCT05732805).

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Section: Discussionunclassified

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

Samoylenko,

Demidov,

Moiseenko

et al. 2023

J. Mod. Onco.

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“…Пролголимаб является высокоаффинным антителом к PD-1-рецеп тору, при ингибировании которого осуществляется двойная блокада сигнального пути PD-L1 и PD-L2 на опухолевых или иммунных клетках. В результате связывания рецептора PD-1 с его лигандами пролголимаб реактивирует опухоль-специфичные цитотоксические Т-лимфоциты и таким образом реактивирует противоопухолевый иммунитет [11,12].…”

Section: иммунотерапия диссеминированной меланомыunclassified

“…Медиана числа проведенных курсов иммунотерапии составила 11,5 (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”

Section: собственный опытunclassified

“…Стойкая стабилизация стала результатом использования пролголимаба у 5 (45,5%) больных. В настоящее время 4 (36,2%) пациента продолжают иммунотерапию пролголимабом на фоне стойкой стабилизации; медиана полученных курсов составляет 14,25 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”

Section: собственный опытunclassified

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News in immunotherapy for metastatic melanoma: prolgolimab in clinical practice (authors' experience)

Oganesyan,

Karnaukhov,

Feoktistova

2023

J. Mod. Onco.

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The incidence of skin melanoma is growing globally and in Russia. Also, the proportion of patients with advanced skin melanoma prevails. Introduction into clinical practice of a novel group of immunological drugs (anti-CTLA4 and anti-PD-1) for metastatic melanoma increased the time to disease progression and patients' life expectancy. Prolgolimab is a PD-1 inhibitor, a new domestic drug that is effective and safe in treating metastatic melanoma. The article presents authors' experience with prolgolimab. When used in the first-line treatment of metastatic melanoma, this drug achieved long-term stabilization of the disease. The drug showed good tolerability, including in patients with severe comorbidity.

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Emerging PD-1/PD-L1 antagonists for the treatment of malignant melanoma

Vanella

Festino

Vitale

et al. 2021

Expert Opinion on Emerging Drugs

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Final Results of Phase II Trial (MIRACULUM) of the Novel PD-1 Inhibitor Prolgolimab in Patients with Advanced Melanoma

Cited by 4 publications

References 0 publications

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

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

News in immunotherapy for metastatic melanoma: prolgolimab in clinical practice (authors' experience)

Emerging PD-1/PD-L1 antagonists for the treatment of malignant melanoma

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