Clinical trial NCT05732805: 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
Official title: A Double-Blind Placebo-Controlled Comparative Randomized Clinical Study of the Efficacy and Safety 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Melanoma
Melanoma (Skin)
Melanoma Stage III
Melanoma Stage IV
Melanoma Unresectable
Melanoma Metastatic
Melanoma Advanced
Keywords: PD-1
CTLA-4
prolgolimab
nurulimab
immunotherapy
checkpoint inhibitors
CPI
programm death
cytotoxic T-lymphocyte-associated protein
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2023-02-17
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

Eligibility criteria: Inclusion Criteria:

1. Signed informed consent and the subject's ability to comply with the requirements of the clinical study protocol;
2. Age ≥18 years at the time of signing the informed consent form;
3. Histologically confirmed melanoma (with available documented evidence of relevant investigations);
4. Untreated unresectable stage III melanoma or untreated metastatic (stage IV) melanoma;
5. Available blocks for histological examination and/or the subject's consent to undergo biopsy ;
6. Consent to the evaluation of the PD-L1 status and BRAF V600 mutation status at a central laboratory;
7. ECOG score 0-1;
8. Life expectancy of at least 12 weeks ;
9. Measurable target tumor lesions (at least 1 lesion) according to RECIST 1.1 criteria , confirmed by central independent reviewer;
10. 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:

1. Indications for radical (surgical, radiation) therapy;
2. A history of previous systemic antitumor therapy for unresectable or metastatic melanoma ;
3. Prior therapy with checkpoint inhibitors (e.g., anti-CTLA-4 and/or anti-PD-1/PD-L1/PD-L2 products);
4. Prior therapy with BRAF and MEK protein kinase inhibitors;
5. Use of immunostimulants, monoclonal antibodies and/or colony-stimulating factors within less than 4 weeks prior to randomization in the study;
6. Ocular melanoma;
7. Mucosal melanoma;
8. CNS metastases;
9. Impossibility to determine PD-L1 status and/or BRAF status;
10. 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;
11. 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;
12. 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.) ;
13. History of interstitial pulmonary disease or pneumonitis requiring systemic glucocorticoids;
14. 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;
15. Hematologic abnormalities :

    * neutrophils \<1.5×109/L;
    * platelets \<100×109/L;
    * hemoglobin \<90 g/L;
16. Renal impairment: creatinine ≥2.5×ULN;
17. 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);
18. Any antitumor treatment within less than 4 weeks or surgery within less than 28 days prior to randomization within the study;
19. History of oncological disease, except for radically treated diseases with remission for over 5 years prior randomization in this study ;
20. Conditions limiting the subject's ability to comply with the Protocol requirements (in the Investigator's opinion );
21. Participation in other clinical studies within less than 30 days prior to randomization and during this clinical study ;
22. Acute infections or activation of chronic infectious diseases or systemic antibacterial therapy within less than 28 days prior to randomization;
23. Active hepatitis B, active hepatitis C (confirmed by PCR), active syphilis, HIV-infection, currently or previously ;
24. Impossibility to administer the investigational product intravenously;
25. Impossibility to administer intravenous contrast agents (including due to hypersensitivity to contrast media);
26. Hypersensitivity to any of the components of BCD-100 or BCD-217;
27. A history of hypersensitivity to monoclonal antibody products;
28. Pregnancy or breastfeeding.

Primary outcomes:
measure: Progression-free survival
timeFrame: 24 months
Secondary outcomes:
measure: Overall survival
timeFrame: 24 months
measure: Overall response rate (partial response + complete response rate)
timeFrame: 24 months
measure: Disease control rate (stable disease + partial response + complete response rate)
timeFrame: 24 months
measure: Time to response
timeFrame: 24 months
measure: Duration of response
timeFrame: 24 months
measure: The proportion of subjects experiencing adverse events related to study therapy
timeFrame: 24 months
measure: The proportion of subjects experiencing any grade 3 or higher adverse events
timeFrame: 24 months
measure: The proportion of subjects with SAEs
timeFrame: 24 months
measure: The proportion of subjects with immune-related adverse events of any severity
timeFrame: 24 months
measure: The proportion of subjects with severe immune-related adverse events
timeFrame: 24 months
measure: The proportion of subjects requiring treatment discontinuation due to AEs
timeFrame: 24 months
measure: The proportion of BAb and NAb positive subjects
timeFrame: 24 months
measure: Ctrough (plasma concentration of anti-PD-1/CTLA-4 monoclonal antibody measured at the end of the dosing interval before the next dose)
timeFrame: 24 months
Other outcomes:
Locations:
city: Babruysk
country: Belarus
facility: Healthcare Institution "Bobruisk Interdistrict Oncological Dispensary"
city: Brest
country: Belarus
facility: Healthcare Institution "Brest Regional Oncological Dispensary"
city: Gomel
country: Belarus
facility: Health Institution "Gomel Regional Clinical Oncology Center"
city: Grodno
country: Belarus
facility: Health care institution "Grodno University Clinic"
city: Lesnoy
country: Belarus
facility: State Institution "Republican Scientific and Practical Center of Oncology and Medical Radiology named after A.I. N.N. Alexandrov"
city: Minsk
country: Belarus
facility: Healthcare Institution "Minsk City Clinical Cancer Center"
city: Mogilev
country: Belarus
facility: State Institution "Mogilev Regional Oncological Dispensary"
city: Vitebsk
country: Belarus
facility: Healthcare Institution "Vitebsk Regional Clinical Oncology Center"
city: Faridabad
country: India
facility: Fortis Hospital
city: Mangalore
country: India
facility: Kasturba Medical College and Hospital
city: Mumbai
country: India
facility: TATA Memorial Hospital
city: Nagpur
country: India
facility: HealthCare Global Enterprises Ltd, NCHRI Cancer Center
city: Nashik
country: India
facility: HealthCare Global Enterprises Ltd Manavata cancer Centre
city: Nashik
country: India
facility: Sankalp Superspeciality Hospital
city: New Delhi
country: India
facility: All India Institute of Medical Science
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital & Research Center
city: Pune
country: India
facility: PDEAS Ayurved Rugnalaya & Steriling Multispeciality Hospital
city: Sangli
country: India
facility: Horizon Mulitispeciality Hospital
city: Surat
country: India
facility: Shalby Hospital
city: Sūrat
country: India
facility: Kiran Multispeciality hospital &Research
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine
state: Chelyabinsk Oblast
city: Pyatigorsk
country: Russian Federation
facility: LLC "New Clinic"
state: Stavropol Krai
city: Arkhangel'sk
country: Russian Federation
facility: Arkhangelsk Clinical Oncology Dispensary
city: Barnaul
country: Russian Federation
facility: Regional State Budgetary Institution of Health Care "Altai Regional Oncological Dispensary"
city: Chelyabinsk
country: Russian Federation
facility: Limited Liability Company "EVIMED"
city: Chelyabinsk
country: Russian Federation
facility: Private healthcare institution "Clinical hospital "RZD-Medicine" of the city of Chelyabinsk"
city: Gatchina
country: Russian Federation
facility: State budgetary healthcare institution Leningrad Regional Clinical Hospital
city: Kazan
country: Russian Federation
facility: State Autonomous Health Institution "Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of Tatarstan named after Professor M.Z. Sigal"
city: Kemerovo
country: Russian Federation
facility: State budgetary health care institution "Kuzbass clinical oncological dispensary named after M.S. Rappoport"
city: Kostroma
country: Russian Federation
facility: Regional Goverment Budgetary Healthcare State "Kostroma Oncology Center"
city: Kuz'molovskiy
country: Russian Federation
facility: State Budgetary Institution of Healthcare "Leningrad Regional Clinical Oncological Dispensary named after V.I. L.D. Romana"
city: Moscow
country: Russian Federation
facility: "Russian Cancer Research Center named after N.N. Blokhin "of the Ministry of Health of the Russian Federation
city: Moscow
country: Russian Federation
facility: Branch of Hadassah Medical LTD Limited Liability Company
city: Moscow
country: Russian Federation
facility: 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)
city: Moscow
country: Russian Federation
facility: Joint Stock Company "K31 City"
city: Moscow
country: Russian Federation
facility: JSC "Medsi Group"
city: Moscow
country: Russian Federation
facility: Moscow City Oncology Hospital No. 62
city: Moscow
country: Russian Federation
facility: 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"
city: Moscow
country: Russian Federation
facility: 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"
city: Nizhny Novgorod
country: Russian Federation
facility: Nizhny Novgorod Region State Budgetary Healthcare Facility "Clinical Diagnostics Center"
city: Novosibirsk
country: Russian Federation
facility: LLC "DobroMed"
city: Novosibirsk
country: Russian Federation
facility: State Budgetary Healthcare Institution "Novosibirsk Regional Clinical Oncology Center" of the Novosibirsk Region
city: Obninsk
country: Russian Federation
facility: Federal State Budgetary Institution "National Medical Research Center for Radiology" of the Ministry of Health of the Russian Federation
city: Omsk
country: Russian Federation
facility: Budgetary Healthcare Institution of Omsk Region "Clinical Oncology Center"
city: Pesochnyy
country: Russian Federation
facility: 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
city: Saint Petersburg
country: Russian Federation
facility: LLC "Clinical Trials"
city: Saint Petersburg
country: Russian Federation
facility: JSC "Modern Medical Technologies"
city: Saint Petersburg
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Saint Petersburg State University"
city: Saint Petersburg
country: Russian Federation
facility: Federal State Budgetary Health Institution St. Petersburg Clinical Hospital of the Russian Academy of Sciences
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "EuroCityClinic"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Oncological Research Center"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Stepmed Clinic"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Strategic Medical Systems"
city: Saint Petersburg
country: Russian Federation
facility: LLC "AV medical group"
city: Saint Petersburg
country: Russian Federation
facility: N.N. Petrov National Medicine Research Center of oncology
city: Saint Petersburg
country: Russian Federation
facility: Private Medical Institution Evromedservis
city: Samara
country: Russian Federation
facility: Private institution educational organization of higher education "Medical University "Reaviz"
city: Sankt Petersburg
country: Russian Federation
facility: State budgetary health care institution "St. Petersburg Clinical Scientific and Practical Center of Specialized Medical Assistance (Oncological)"
city: Saransk
country: Russian Federation
facility: Federal State Educational Institution of Higher Professional Education "Mordovia State University N.P. Ogareva "
city: Sochi
country: Russian Federation
facility: Oncology Dispensary 2
city: St. Petersburg
country: Russian Federation
facility: City Hospital #40, Kurortny district
city: Volgograd
country: Russian Federation
facility: State Health Care Institution "Volgograd Regional Clinical Oncology Dispensary № 1"
city: Yaroslavl
country: Russian Federation
facility: State Regional Budgetary Healthcare Institution "Regional Clinical Oncology Hospital" of the Yaroslavl Region
Study officials:
References: