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

Melanoma Clinical Trial

— OCTAVA  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05732805
• Other study ID #: BCD-217-2
• Status: Recruiting
• Phase: Phase 3
• Start date: August 2, 2022
• Est. completion date: April 2025

Study information

• Verified date: February 2023
• Source: Biocad
• Contact: Anna A Siliutina, MD PhD
• Phone: +7 (812) 380 49 33
• Email: siljutina[@]biocad.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 270
• Est. completion date: April 2025
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)
• Melanoma Metastatic
• Melanoma Stage III
• Melanoma Stage IV

Intervention

Biological:
• BCD-217
Subject recieves BCD-217 0.2 mL/kg, which is equivalent to 1 mg/kg nurulimab + 3 mg/kg prolgolimab, as an intravenous infusion once every 3 weeks (Q3W) simultaneously with placebo, a total of 4 intravenous infusions. Beginning with the 5th infusion, subjects are switched to prolgolimab 1 mg/kg monotherapy once every 2 weeks (Q2W).
• BCD-100
Subject recieves prolgolimab 3 mg/kg as an intravenous infusion once every 3 weeks (Q3W) simultaneously with placebo, a total of 4 intravenous infusions. Beginning with the 5th infusion, subjects are switched to prolgolimab 1 mg/kg monotherapy once every 2 weeks (Q2W).
• Placebo
Placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Biocad

Countries where clinical trial is conducted

Belarus,  India,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		24 months
Secondary	Overall survival		24 months
Secondary	Overall response rate (partial response + complete response rate)		24 months
Secondary	Disease control rate (stable disease + partial response + complete response rate)		24 months
Secondary	Time to response		24 months
Secondary	Duration of response		24 months
Secondary	The proportion of subjects experiencing adverse events related to study therapy		24 months
Secondary	The proportion of subjects experiencing any grade 3 or higher adverse events		24 months
Secondary	The proportion of subjects with SAEs		24 months
Secondary	The proportion of subjects with immune-related adverse events of any severity		24 months
Secondary	The proportion of subjects with severe immune-related adverse events		24 months
Secondary	The proportion of subjects requiring treatment discontinuation due to AEs		24 months
Secondary	The proportion of BAb and NAb positive subjects		24 months
Secondary	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