A Study of Neoadjuvant Therapy With BCD-217 (Nurulimab + Prolgolimab) in Patients With Resectable Stage III Skin Melanoma

Melanoma (Skin) Clinical Trial

— NEO-MIMAJOR  

Official title:

A Randomized Study of the Efficacy and Safety of Neoadjuvant Therapy With BCD-217 (Nurulimab + Prolgolimab) Versus Standard Adjuvant Therapy With Pembrolizumab in Patients With Resectable Stage III Skin Melanoma.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05751928
• Other study ID #: BCD-217-3
• Status: Recruiting
• Phase: Phase 3
• Start date: March 2023
• Est. completion date: June 2027

Study information

• Verified date: March 2023
• Source: Biocad
• Contact: Fedor B Kriukov, MD PhD
• Phone: +7 (812) 380 49 33
• Email: biocad[@]biocad.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is an open-label, randomized, comparative phase III study, which will include subjects with resectable stage III skin melanoma (up to 3 resectable transient metastases are acceptable).

Description:

In both study groups, adjuvant therapy is possible until melanoma progresses to unresectable stage III-IV, unacceptable toxicity, withdrawal of ICF or the end of the therapy period (12 months). In case of postoperative relapse of the disease, at the decision of the investigator and if the lesion is resectable, radical surgical treatment can be carried out (R0 - resection) in accordance with current clinical guidelines without withdrawing the patient from the study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 410
• Est. completion date: June 2027
• Est. primary completion date: January 2027
• 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 or cytologically confirmed (documented results of relevant studies are available) resectable stage IIIB/C/D skin melanoma;

4. At least one clinically detectable lymph node accessible for biopsy and not more than three resectable in-transit metastases .

Clinically detectable lymph nodes include:

• Palpable lymph nodes with pathologically confirmed melanoma
• Non-palpable but enlarged (=15 mm in smallest diameter, RECIST 1.1) lymph nodes with pathologically confirmed melanoma

5. Subject's consent to a biopsy;

6. Consent to the evaluation of the PD-L1 status and BRAF V600 mutation status ;

7. ECOG score 0-1;

8. Life expectancy of at least 5 years;

9. Willingness of subjects and their sexual partners of childbearing potential to use reliable methods of contraception from the date of signing the informed consent form throughout the study period and for 24 weeks after the administration of the last dose of the investigational therapy.

Exclusion Criteria:

1. Ocular melanoma;

2. Mucosal melanoma;

3. Distant metastases;

4. Impossibility of radical resection of the tumor, metastasis and/or involved lymph nodes;

5. Presence of only in-transit transit/satellite metastases without confirmed involvement of lymph nodes;

6. Prior therapy with checkpoint inhibitors (e.g. anti-CTLA-4 and/or anti-PD-1/PD-L1/PD-L2 products);

7. Prior therapy with BRAF and MEK protein kinase inhibitors;

8. Prior radiation therapy;

9. Inability to determine BRAF status;

10. Subjects with severe comorbidities, with life-threatening acute complications of the underlying disease at the time of signing the informed consent form;

11. Current concomitant diseases at the time of screening, which increase the risk of severe adverse events during surgery and/or study therapy administration;

• 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 cardiac failure (NYHA classes III and IV);
• uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg) ;
• a history of atopic asthma , angioneurotic edema;
• 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 surgery or study therapy;

12. Known or suspected systemic autoimmune diseases (including, but not limited to, systemic lupus erythematosus, Crohn's disease, ulcerative colitis (UC), systemic scleroderma, inflammatory myopathy, mixed connective tissue disease, overlap syndrome, etc.) ;

13. A history of interstitial pulmonary disease or pneumonitis requiring systemic glucocorticoids;

14. The need for glucocorticoid therapy (at >10mg/day prednisolone equivalent doses) or any other drugs with immunosuppressive effects within 6 months prior to randomization;

15. Use of immunostimulants, monoclonal antibodies and/or colony-stimulating factors within less than 4 weeks prior to randomization in the study;

16. Hematological abnormalities :

• neutrophils <1.5×109/L;
• platelets <100×109/L;
• hemoglobin <90 g/L;

17. Renal impairment: creatinine =1.5×ULN;

18. Hepatic impairment :

• Total bilirubin =1.3×ULN (except for subjects with Gilbert's syndrome, in whom bilirubin levels should not exceed 50 µmol/L);
• ALP, AST or ALT =1.5×ULN;

19. Any surgery within less than 28 days prior to randomization in the study;

20. History of oncological disease, except for radically treated diseases with remission for over 5 years prior randomization in this study ;

21. Conditions limiting the subject's ability to comply with the Protocol requirements (in the Investigator's opinion );

22. Participation in other clinical studies within less than 30 days prior to randomization and during this clinical study ;

23. Acute infections or activation of chronic infectious diseases or systemic antibacterial therapy within less than 28 days prior to randomization;

24. Active hepatitis B, active hepatitis C (confirmed by PCR), HIV-infection, currently or previously ;

25. Impossibility to administer the investigational product intravenously;

26. Impossibility to administer intravenous contrast agents (including due to hypersensitivity to contrast media);

27. Hypersensitivity to any of the components of BCD-217, prolgolimab or pembrolizumab;

28. A history of hypersensitivity to monoclonal antibody products;

29. Pregnancy or breastfeeding.

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)
• Melanoma Stage III

Intervention

Biological:
• BCD-217
BCD-217 (anti-CTLA4 agent nurulimab + anti-PD1) once every 3 weeks in the neoadjuvant setting
• anti-PD1
anti-PD1 agent in the adjuvant setting

Procedure:
• Excision of the primary lesion
Excision of the primary lesion will be performed per standard of care.
• Regional lymphadenectomy
Regional lymphadenectomy will be performed per standard of care.

Locations

Country	Name	City	State
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
Russian Federation	State Budgetary Healthcare Institution "Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine",	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	Clinical Oncologic Dispensary No. 1	Krasnodar	Krasnodar Kari
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	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 the Omsk region "Clinical oncological dispensary"	Omsk
Russian Federation	Federal State Budgetary Educational Institution of Higher Education "Saint Petersburg State University"	Saint Petersburg
Russian Federation	JSC "Modern Medical Technologies"	Saint Petersburg
Russian Federation	Limited Liability Company "American Medical Clinic"	Saint Petersburg
Russian Federation	Limited Liability Company "Oncological Research Center"	Saint Petersburg
Russian Federation	Limited Liability Company "Strategic Medical Systems"	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	Saint-Petersburg Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)	Saint Petersburg
Russian Federation	Federal State Educational Institution of Higher Professional Education "Mordovia State University N.P. Ogareva "	Saransk
Russian Federation	Clinical Oncologic Dispensary No. 2	Sochi	Krasnodar Territory
Russian Federation	City Hospital #40, Kurortny district	St. Petersburg
Russian Federation	State Health Care Institution "Volgograd Regional Clinical Oncology Dispensary ? 1"	Volgograd
Russian Federation	Regional Clinical Oncology Hospital	Yaroslavl	Yaroslavskaya Oblast

Sponsors (1)

Lead Sponsor	Collaborator
Biocad

Countries where clinical trial is conducted

Belarus,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	event free survival (EFS)		24 months
Secondary	overall survival (OS)		24 months
Secondary	distant metastases-free survival (DMFS)		24 months
Secondary	pathologic response rate (pRR)		24 months
Secondary	The proportion of subjects with treatment-related adverse events;		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 (grade 3 or higher according to CTCAE v.5.0)		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