Clinical trial NCT05751928: A Study of Neoadjuvant Therapy With BCD-217 (Nurulimab + Prolgolimab) in Patients With Resectable Stage III Skin Melanoma
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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Melanoma Stage III
Melanoma (Skin)
Keywords: PD-1
CTLA-4
prolgolimab
nurulimab
immunotherapy
checkpoint inhibitors
CPI
programm death
cytotoxic T-lymphocyte-associated protein
Neoadjuvant Melanoma
Adjuvant Melanoma
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2023-03-02
Enrollment: 410
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: 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).

Detailed 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.

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 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.

Primary outcomes:
measure: event free survival (EFS)
timeFrame: 24 months
Secondary outcomes:
measure: overall survival (OS)
timeFrame: 24 months
measure: distant metastases-free survival (DMFS)
timeFrame: 24 months
measure: pathologic response rate (pRR)
timeFrame: 24 months
measure: The proportion of subjects with treatment-related adverse events;
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 (grade 3 or higher according to CTCAE v.5.0)
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
Other outcomes:
Locations:
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: Krasnodar
country: Russian Federation
facility: Clinical Oncologic Dispensary No. 1
state: Krasnodar Kari
city: Sochi
country: Russian Federation
facility: Clinical Oncologic Dispensary No. 2
state: Krasnodar Territory
city: Yaroslavl
country: Russian Federation
facility: Regional Clinical Oncology Hospital
state: Yaroslavskaya Oblast
city: Chelyabinsk
country: Russian Federation
facility: State Budgetary Healthcare Institution "Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine",
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: 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 the Omsk region "Clinical oncological dispensary"
city: Saint Petersburg
country: Russian Federation
facility: JSC "Modern Medical Technologies"
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)
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: Limited Liability Company "American Medical Clinic"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Oncological Research Center"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Strategic Medical Systems"
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: Saransk
country: Russian Federation
facility: Federal State Educational Institution of Higher Professional Education "Mordovia State University N.P. Ogareva "
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"
Study officials:
References: