A Clinical Study of BCD-217 (Nurulimab + Prolgolimab) Followed by Anti-PD-1 Compared to Anti-PD-1 Monotherapy as First-Line Treatment in Subjects With Unresectable/Metastatic Melanoma

Phase 3

Recruiting

Conditions: Melanoma
Melanoma Stage III
Melanoma (Skin)
Melanoma Stage IV
Melanoma Unresectable
Melanoma Metastatic
Melanoma Advanced

Interventions: Biological: BCD-217
Biological: BCD-100
Biological: Placebo

Registration Number: NCT05732805

Lead Sponsor: Biocad

Brief Summary: The aim of study is to investigate the efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics of BCD-217 followed by prolgolimab monotherapy versus prolgolimab monotherapy as first-line therapy in subjects with unresectable or metastatic melanoma.

Detailed Description: This study is designed as a phase III, randomized, double-blind, placebo-controlled study.

After the stratification procedure, subjects are randomized in a 1:1 ratio into 2 groups:

* BCD-217 + placebo (4 doses) → prolgolimab (BCD-217 group)

* Prolgolimab + placebo (4 doses) → prolgolimab (BCD-100 monotherapy group)

Recruitment & Eligibility

Status: RECRUITING

Sex: All

Target Recruitment: 270

Inclusion Criteria

Signed informed consent and the subject's ability to comply with the requirements of the clinical study protocol;
Age ≥18 years at the time of signing the informed consent form;
Histologically confirmed melanoma (with available documented evidence of relevant investigations);
Untreated unresectable stage III melanoma or untreated metastatic (stage IV) melanoma;
Available blocks for histological examination and/or the subject's consent to undergo biopsy ;
Consent to the evaluation of the PD-L1 status and BRAF V600 mutation status at a central laboratory;
ECOG score 0-1;
Life expectancy of at least 12 weeks ;
Measurable target tumor lesions (at least 1 lesion) according to RECIST 1.1 criteria , confirmed by central independent reviewer;
In subjects of childbearing potential, willingness to use reliable contraceptive measures throughout the study, from the signing of the informed consent form and for additional 24 weeks after the administration of the last dose of the investigational product.

Exclusion Criteria

Indications for radical (surgical, radiation) therapy;
A history of previous systemic antitumor therapy for unresectable or metastatic melanoma ;
Prior therapy with checkpoint inhibitors (e.g., anti-CTLA-4 and/or anti-PD-1/PD-L1/PD-L2 products);
Prior therapy with BRAF and MEK protein kinase inhibitors;
Use of immunostimulants, monoclonal antibodies and/or colony-stimulating factors within less than 4 weeks prior to randomization in the study;
Ocular melanoma;
Mucosal melanoma;
CNS metastases;
Impossibility to determine PD-L1 status and/or BRAF status;
Subjects with severe comorbidities, life-threatening acute complications of the primary disease (including massive pleural, pericardial, or peritoneal effusions requiring intervention , pulmonary lymphangitis, bleeding, or organ perforation) at the time of signing the informed consent form;
Ongoing concomitant diseases at the time of screening, which increase the risk of severe adverse events during the administration of the study therapy:
- stable angina, functional class III-IV;
- unstable angina or a history of myocardial infarction within less than 6 months prior to signing the informed consent form;
- moderate to severe heart failure (classes III and IV according to NYHA classification);
- uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg) ;
- a history of atopic asthma , angioedema;
- respiratory failure (moderate to severe), grade 3 or 4 chronic obstructive pulmonary disease;
- any other concomitant diseases (including, but not limited to, metabolic, hematological, renal, hepatic, pulmonary, neurological, endocrine, cardiac, infectious, gastrointestinal disorders), which expose the subject to an unacceptable risk during the study therapy;
Known or suspected systemic autoimmune diseases (including, but not limited to, systemic lupus erythematosus, Crohn's disease, nonspecific ulcerative colitis, systemic scleroderma, inflammatory myopathy, mixed connective tissue disease, overlap syndrome, etc.) ;
History of interstitial pulmonary disease or pneumonitis requiring systemic glucocorticoids;
The need for glucocorticoid therapy (at >10 mg/day prednisolone equivalent doses) or any other drugs with immunosuppressive effects within 14 days prior to randomization;
Hematologic abnormalities :
- neutrophils <1.5×109/L;
- platelets <100×109/L;
- hemoglobin <90 g/L;
Renal impairment: creatinine ≥2.5×ULN;
Hepatic impairment :
- total bilirubin ≥3×ULN (except for subjects with Gilbert's syndrome, in whom bilirubin levels should not exceed 50 μmol/L),
- AP, AST or ALT ≥2.5×ULN (≥5×ULN in case of subjects with liver metastases);
Any antitumor treatment within less than 4 weeks or surgery within less than 28 days prior to randomization within the study;
History of oncological disease, except for radically treated diseases with remission for over 5 years prior randomization in this study ;
Conditions limiting the subject's ability to comply with the Protocol requirements (in the Investigator's opinion );
Participation in other clinical studies within less than 30 days prior to randomization and during this clinical study ;
Acute infections or activation of chronic infectious diseases or systemic antibacterial therapy within less than 28 days prior to randomization;
Active hepatitis B, active hepatitis C (confirmed by PCR), active syphilis, HIV-infection, currently or previously ;
Impossibility to administer the investigational product intravenously;
Impossibility to administer intravenous contrast agents (including due to hypersensitivity to contrast media);
Hypersensitivity to any of the components of BCD-100 or BCD-217;
A history of hypersensitivity to monoclonal antibody products;
Pregnancy or breastfeeding.

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BCD-217 (nurulimab + prolgolimab)	BCD-100	BCD-217 followed by prolgolimab 1 mg/kg monotherapy.
BCD-100 (prolgolimab)	Placebo	Prolgolimab monotherapy.
BCD-217 (nurulimab + prolgolimab)	BCD-217	BCD-217 followed by prolgolimab 1 mg/kg monotherapy.
BCD-217 (nurulimab + prolgolimab)	Placebo	BCD-217 followed by prolgolimab 1 mg/kg monotherapy.
BCD-100 (prolgolimab)	BCD-100	Prolgolimab monotherapy.

Primary Outcome Measures

Name	Time	Method
Progression-free survival	24 months

Secondary Outcome Measures

Name	Time	Method
The proportion of subjects experiencing adverse events related to study therapy	24 months
The proportion of subjects experiencing any grade 3 or higher adverse events	24 months
The proportion of subjects with SAEs	24 months
The proportion of subjects with immune-related adverse events of any severity	24 months
The proportion of BAb and NAb positive subjects	24 months
Duration of response	24 months
Time to response	24 months
Overall survival	24 months
The proportion of subjects requiring treatment discontinuation due to AEs	24 months
Ctrough (plasma concentration of anti-PD-1/CTLA-4 monoclonal antibody measured at the end of the dosing interval before the next dose)	24 months
Overall response rate (partial response + complete response rate)	24 months
Disease control rate (stable disease + partial response + complete response rate)	24 months
The proportion of subjects with severe immune-related adverse events	24 months

Trial Locations

Locations (63): Healthcare Institution "Bobruisk Interdistrict Oncological Dispensary"
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Babruysk, Belarus
Healthcare Institution "Vitebsk Regional Clinical Oncology Center"
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Vitebsk, Belarus
Health Institution "Gomel Regional Clinical Oncology Center"
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Gomel, Belarus
Health care institution "Grodno University Clinic"
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Grodno, Belarus
State Institution "Republican Scientific and Practical Center of Oncology and Medical Radiology named after A.I. N.N. Alexandrov"
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Lesnoy, Belarus
TATA Memorial Hospital
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Mumbai, India
Federal State Budgetary Educational Institution of Higher Education "Saint Petersburg State University"
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Saint Petersburg, Russian Federation
LLC "DobroMed"
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Novosibirsk, Russian Federation
State Budgetary Institution of Healthcare of the City of Moscow "Moscow Multidisciplinary Clinical Center "Kommunarka" of the Department of Health of the City of Moscow"
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Moscow, Russian Federation
LLC "New Clinic"
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Pyatigorsk, Stavropol Krai, Russian Federation
Moscow City Oncology Hospital No. 62
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Moscow, Russian Federation
State budgetary health care institution of the city of Moscow "City Clinical Oncology Hospital No. 1 of the Department of Health of the City of Moscow"
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Moscow, Russian Federation
State Budgetary Healthcare Institution "Novosibirsk Regional Clinical Oncology Center" of the Novosibirsk Region
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Novosibirsk, Russian Federation
Limited Liability Company "EuroCityClinic"
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Saint Petersburg, Russian Federation
Limited Liability Company "Oncological Research Center"
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Saint Petersburg, Russian Federation
Limited Liability Company "Stepmed Clinic"
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Saint Petersburg, Russian Federation
LLC "AV medical group"
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Saint Petersburg, Russian Federation
Private institution educational organization of higher education "Medical University "Reaviz"
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Samara, Russian Federation
State budgetary health care institution "St. Petersburg Clinical Scientific and Practical Center of Specialized Medical Assistance (Oncological)"
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Sankt Petersburg, Russian Federation
City Hospital #40, Kurortny district
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St. Petersburg, Russian Federation
State Health Care Institution "Volgograd Regional Clinical Oncology Dispensary № 1"
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Volgograd, Russian Federation
Federal State Educational Institution of Higher Professional Education "Mordovia State University N.P. Ogareva "
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Saransk, Russian Federation
Oncology Dispensary 2
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Sochi, Russian Federation
Healthcare Institution "Brest Regional Oncological Dispensary"
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Brest, Belarus
Healthcare Institution "Minsk City Clinical Cancer Center"
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Minsk, Belarus
State Institution "Mogilev Regional Oncological Dispensary"
🇧🇾
Mogilev, Belarus
Fortis Hospital
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Faridabad, India
HealthCare Global Enterprises Ltd, NCHRI Cancer Center
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Nagpur, India
Kasturba Medical College and Hospital
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Mangalore, India
Sankalp Superspeciality Hospital
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Nashik, India
HealthCare Global Enterprises Ltd Manavata cancer Centre
🇮🇳
Nashik, India
PDEAS Ayurved Rugnalaya & Steriling Multispeciality Hospital
🇮🇳
Pune, India
All India Institute of Medical Science
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New Delhi, India
Deenanath Mangeshkar Hospital & Research Center
🇮🇳
Pune, India
Horizon Mulitispeciality Hospital
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Sangli, India
Shalby Hospital
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Surat, India
Kiran Multispeciality hospital &Research
🇮🇳
Sūrat, India
Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine
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Chelyabinsk, Chelyabinsk Oblast, Russian Federation
Regional State Budgetary Institution of Health Care "Altai Regional Oncological Dispensary"
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Barnaul, Russian Federation
Private healthcare institution "Clinical hospital "RZD-Medicine" of the city of Chelyabinsk"
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Chelyabinsk, Russian Federation
State budgetary healthcare institution Leningrad Regional Clinical Hospital
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Gatchina, Russian Federation
Arkhangelsk Clinical Oncology Dispensary
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Arkhangel'sk, Russian Federation
Limited Liability Company "EVIMED"
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Chelyabinsk, Russian Federation
State Autonomous Health Institution "Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of Tatarstan named after Professor M.Z. Sigal"
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Kazan, Russian Federation
State budgetary health care institution "Kuzbass clinical oncological dispensary named after M.S. Rappoport"
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Kemerovo, Russian Federation
Regional Goverment Budgetary Healthcare State "Kostroma Oncology Center"
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Kostroma, Russian Federation
State Budgetary Institution of Healthcare "Leningrad Regional Clinical Oncological Dispensary named after V.I. L.D. Romana"
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Kuz'molovskiy, Russian Federation
"Russian Cancer Research Center named after N.N. Blokhin "of the Ministry of Health of the Russian Federation
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Moscow, Russian Federation
Branch of Hadassah Medical LTD Limited Liability Company
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Moscow, Russian Federation
Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
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Moscow, Russian Federation
Joint Stock Company "K31 City"
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Moscow, Russian Federation
JSC "Medsi Group"
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Moscow, Russian Federation
Nizhny Novgorod Region State Budgetary Healthcare Facility "Clinical Diagnostics Center"
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Nizhny Novgorod, Russian Federation
Budgetary Healthcare Institution of Omsk Region "Clinical Oncology Center"
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Omsk, Russian Federation
Federal State Budgetary Institution "National Medical Research Center for Radiology" of the Ministry of Health of the Russian Federation
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Obninsk, Russian Federation
Federal State Budgetary Institution "National Medical Research Center of Oncology named after N.N. Petrov" of the Ministry of Health of the Russian Federation (FSBI "N.N. Petrov National Medical Research Center of Oncology" of the Ministry of Health of Ru
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Pesochnyy, Russian Federation
JSC "Modern Medical Technologies"
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Saint Petersburg, Russian Federation
LLC "Clinical Trials"
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Saint Petersburg, Russian Federation
Federal State Budgetary Health Institution St. Petersburg Clinical Hospital of the Russian Academy of Sciences
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Saint Petersburg, Russian Federation
Limited Liability Company "Strategic Medical Systems"
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Saint Petersburg, Russian Federation
N.N. Petrov National Medicine Research Center of oncology
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Saint Petersburg, Russian Federation
Private Medical Institution Evromedservis
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Saint Petersburg, Russian Federation
State Regional Budgetary Healthcare Institution "Regional Clinical Oncology Hospital" of the Yaroslavl Region
🇷🇺
Yaroslavl, Russian Federation

A Clinical Study of BCD-217 (Nurulimab + Prolgolimab) Followed by Anti-PD-1 Compared to Anti-PD-1 Monotherapy as First-Line Treatment in Subjects With Unresectable/Metastatic Melanoma

Recruitment & Eligibility

Study & Design

Trial Locations

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