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
- Authors: Samoylenko I.V.1, Demidov L.V.1, Moiseenko F.V.2,3, Dvorkin M.V.4, Demidova S.A.5, Protsenko S.A.2, Stroyakovskiy D.L.6, Kozlov V.V.7,8, Odintsova S.V.9,10, Kirtbaya D.V.11, Tantsyrev D.A.12, Mochalova A.S.13, Orlova R.V.14,15, Mukhametshina G.Z.16, Fadeeva N.V.17, Fomin E.A.18, Chapko Y.S.19, Tarasova A.V.20, Ermakov N.B.21, Shemerovskiy A.K.22, Vaschenko V.A.23, Chistyakov V.M.24, Zinkina-Orikhan A.V.25, Lin'kova Y.N.25, Kryukov F.B.25, Sorokina I.V.26,25, Siliutina A.A.25
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Affiliations:
- Blokhin National Medical Research Center of Oncology
- Petrov National Medical Research Center of Oncology
- Saint Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)
- Clinical Oncologic Dispensary
- Minsk City Clinical Oncology Center
- Moscow City Oncological Hospital №62
- Novosibirsk State Medical University
- Novosibirsk Regional Clinical Oncologic Dispensary
- Pavlov First Saint Petersburg State Medical University
- EuroCityClinic
- Oncologic Dispensary №2
- Altai Regional Oncological Dispensary
- Medsi Group of Companies
- City Clinical Oncologic Dispensary
- Saint Petersburg State University
- Sigal Republican Clin ical Oncologic Dispensary
- Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine
- Bayandin Murmansk Regional Clinical Hospital
- Arkhangelsk Clinical Oncologic Dispensary
- Samara Regional Clinical Oncology Dispensary
- Aleksandrov Republican Scientific and Practical Center of Oncology and Medical Radiology
- AB Medical Group
- Kostroma Oncological Dispensary
- New Clinic
- Biocad
- Loginov Moscow Clinical Scientific Center
- Issue: Vol 25, No 3 (2023)
- Pages: 313-324
- Section: CLINICAL ONCOLOGY
- URL: https://journals.rcsi.science/1815-1434/article/view/148897
- DOI: https://doi.org/10.26442/18151434.2023.3.202463
- ID: 148897
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Abstract
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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##article.viewOnOriginalSite##About the authors
Igor V. Samoylenko
Blokhin National Medical Research Center of Oncology
Author for correspondence.
Email: i.samoylenko@ronc.ru
ORCID iD: 0000-0001-7150-5071
cand. sci. (med.)
Russian Federation, MoscowLev V. Demidov
Blokhin National Medical Research Center of Oncology
Email: editor@omnidoctor.ru
d. sci. (med.), prof.
Russian Federation, MoscowFedor V. Moiseenko
Petrov National Medical Research Center of Oncology; Saint Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)
Email: editor@omnidoctor.ru
ORCID iD: 0000-0003-2544-9042
d. sci. (med.)
Russian Federation, Saint PetersburgMikhail V. Dvorkin
Clinical Oncologic Dispensary
Email: editor@omnidoctor.ru
cand. sci. (med.)
Russian Federation, OmskSvetlana A. Demidova
Minsk City Clinical Oncology Center
Email: editor@omnidoctor.ru
department head
Belarus, MinskSvetlana A. Protsenko
Petrov National Medical Research Center of Oncology
Email: editor@omnidoctor.ru
department head
Russian Federation, Saint PetersburgDaniil L. Stroyakovskiy
Moscow City Oncological Hospital №62
Email: editor@omnidoctor.ru
ORCID iD: 0000-0003-1973-1092
cand. sci. (med.)
Russian Federation, MoscowVadim V. Kozlov
Novosibirsk State Medical University; Novosibirsk Regional Clinical Oncologic Dispensary
Email: editor@omnidoctor.ru
ORCID iD: 0000-0003-3211-5139
cand. sci. (med.)
Russian Federation, NovosibirskSvetlana V. Odintsova
Pavlov First Saint Petersburg State Medical University; EuroCityClinic
Email: editor@omnidoctor.ru
cand. sci. (med.)
Russian Federation, Saint PetersburgDmitry V. Kirtbaya
Oncologic Dispensary №2
Email: editor@omnidoctor.ru
oncologist
Russian Federation, SochiDenis A. Tantsyrev
Altai Regional Oncological Dispensary
Email: editor@omnidoctor.ru
head of the day hospital
Russian Federation, BarnaulAnastasia S. Mochalova
Medsi Group of Companies
Email: editor@omnidoctor.ru
cand. sci. (med.)
Russian Federation, MoscowRashida V. Orlova
City Clinical Oncologic Dispensary; Saint Petersburg State University
Email: editor@omnidoctor.ru
ORCID iD: 0000-0003-4447-9458
d. sci. (med.), prof.
Russian Federation, Saint PetersburgGuzel Z. Mukhametshina
Sigal Republican Clin ical Oncologic Dispensary
Email: editor@omnidoctor.ru
cand. sci. (med.)
Russian Federation, KazanNatalia V. Fadeeva
Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine
Email: 89048082445@mail.ru
ORCID iD: 0000-0003-3923-929X
cand. sci. (med.)
Russian Federation, ChelyabinskEvgeny A. Fomin
Bayandin Murmansk Regional Clinical Hospital
Email: editor@omnidoctor.ru
deputy chief doctor
Russian Federation, MurmanskYana S. Chapko
Arkhangelsk Clinical Oncologic Dispensary
Email: editor@omnidoctor.ru
oncologist
Russian Federation, ArkhangelskAnna V. Tarasova
Samara Regional Clinical Oncology Dispensary
Email: editor@omnidoctor.ru
department head
Russian Federation, SamaraNikolay B. Ermakov
Aleksandrov Republican Scientific and Practical Center of Oncology and Medical Radiology
Email: editor@omnidoctor.ru
cand. sci. (med.)
Belarus, Lesnoy, Minsk districtAlexander K. Shemerovskiy
AB Medical Group
Email: editor@omnidoctor.ru
cand. sci. (med.)
Russian Federation, Saint PetersburgVera A. Vaschenko
Kostroma Oncological Dispensary
Email: editor@omnidoctor.ru
oncologist
Russian Federation, KostromaValery M. Chistyakov
New Clinic
Email: editor@omnidoctor.ru
cand. sci. (med.)
Russian Federation, PyatigorskArina V. Zinkina-Orikhan
Biocad
Email: editor@omnidoctor.ru
ORCID iD: 0000-0002-8499-2232
director
Russian Federation, Saint PetersburgYulia N. Lin'kova
Biocad
Email: editor@omnidoctor.ru
ORCID iD: 0000-0002-5463-1022
cand. sci. (med.)
Russian Federation, Saint PetersburgFedor B. Kryukov
Biocad
Email: editor@omnidoctor.ru
ORCID iD: 0000-0003-0549-7274
phd
Russian Federation, Saint PetersburgIrina V. Sorokina
Loginov Moscow Clinical Scientific Center; Biocad
Email: sorokinaiv@biocad.ru
ORCID iD: 0000-0002-9404-3698
cand. sci. (biol.)
Russian Federation, Moscow; Saint PetersburgAnna A. Siliutina
Biocad
Email: siljutina@biocad.ru
ORCID iD: 0000-0002-4694-4504
cand. sci. (med.)
Russian Federation, Saint PetersburgReferences
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