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

• Sponsor: Biocad (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05751928
• Collaborator: (none)
• Enrollment: 410
• Locations: 36
• Arms: 3
• Anticipated Duration (Months): 51
• Patients Per Site: 11.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Resectable Melanoma; Melanoma Stage III; Melanoma (Skin)	Biological: BCD-217; Biological: anti-PD1; Procedure: Excision of the primary lesion; Procedure: Regional lymphadenectomy	Phase 3

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 410 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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.
• Anticipated Study Start Date: Mar 1, 2023
• Anticipated Primary Completion Date: Jan 1, 2027
• Anticipated Study Completion Date: Jun 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Subjects with pCR and pnCR (Group 1A) Subjects will receive 2 cycles of BCD-217 neoadjuvant therapy, followed by index lymph node removal. Subjects with pathological complete (pCR) and near complete response (pnCR) (Group 1A): excision of the primary lesion (if not previously performed) without regional lymphadenectomy, followed by up to 12 months of anti-PD1 agent in the adjuvant setting.	Biological: BCD-217; BCD-217 (anti-CTLA4 agent nurulimab + anti-PD1) once every 3 weeks in the neoadjuvant setting; Other Names: nurulimab+prolgolimab ; Biological: 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.
Experimental: Subjects with a pPR or pNR to neoadjuvant therapy (Group 1B) Subjects will receive 2 cycles of BCD-217 neoadjuvant therapy, followed by index lymph node removal. Subjects with a pathological partial response (pPR) or non-responders (pNR) to neoadjuvant therapy (Group 1B): excision of the primary lesion (if not performed earlier), regional lymphadenectomy, then up to 12 months of adjuvant therapy with anti-PD1 agent.	Biological: BCD-217; BCD-217 (anti-CTLA4 agent nurulimab + anti-PD1) once every 3 weeks in the neoadjuvant setting; Other Names: nurulimab+prolgolimab ; Biological: 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.; Procedure: Regional lymphadenectomy; Regional lymphadenectomy will be performed per standard of care.
Active Comparator: Control Group (Group 2) Subjects start treatment with excision of the primary lesion (if not previously performed), regional lymphadenectomy followed by adjuvant therapy with anti-PD1 agent (up to 12 months). This approach is considered the standard therapy for patients in the target population.	Procedure: Excision of the primary lesion; Excision of the primary lesion will be performed per standard of care.; Procedure: Regional lymphadenectomy; Regional lymphadenectomy will be performed per standard of care.

Outcome Measures

Primary Outcome Measures

1. event free survival (EFS) [24 months]

Secondary Outcome Measures

1. overall survival (OS) [24 months]

2. distant metastases-free survival (DMFS) [24 months]

3. pathologic response rate (pRR) [24 months]

4. The proportion of subjects with treatment-related adverse events; [24 months]

5. The proportion of subjects experiencing any grade 3 or higher adverse events [24 months]

6. The proportion of subjects with SAEs [24 months]

7. The proportion of subjects with immune-related adverse events of any severity [24 months]

8. The proportion of subjects with severe immune-related adverse events (grade 3 or higher according to CTCAE v.5.0) [24 months]

9. The proportion of subjects requiring treatment discontinuation due to AEs [24 months]

10. The proportion of BAb and NAb positive subjects [24 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. Subject's consent to a biopsy;

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

3. ECOG score 0-1;

4. Life expectancy of at least 5 years;

5. 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;

1. 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.) ;

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

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

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

5. Hematological abnormalities :

• neutrophils <1.5×109/L;

• platelets <100×109/L;

• hemoglobin <90 g/L;

1. Renal impairment: creatinine ≥1.5×ULN;

2. 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;

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

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

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

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

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

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

7. Impossibility to administer the investigational product intravenously;

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

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

10. A history of hypersensitivity to monoclonal antibody products;

11. Pregnancy or breastfeeding.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	State Institution "Republican Scientific and Practical Center of Oncology and Medical Radiology named after A.I. N.N. Alexandrov"	Lesnoy		Belarus
2	Healthcare Institution "Minsk City Clinical Cancer Center"	Minsk		Belarus	220013
3	State Institution "Mogilev Regional Oncological Dispensary"	Mogilev		Belarus
4	Healthcare Institution "Vitebsk Regional Clinical Oncology Center"	Vitebsk		Belarus
5	Clinical Oncologic Dispensary No. 1	Krasnodar	Krasnodar Kari	Russian Federation	350040
6	Clinical Oncologic Dispensary No. 2	Sochi	Krasnodar Territory	Russian Federation	354057
7	Regional Clinical Oncology Hospital	Yaroslavl	Yaroslavskaya Oblast	Russian Federation	150054
8	State Budgetary Healthcare Institution "Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine",	Chelyabinsk		Russian Federation	454087
9	State budgetary healthcare institution Leningrad Regional Clinical Hospital	Gatchina		Russian Federation
10	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
11	State budgetary health care institution "Kuzbass clinical oncological dispensary named after M.S. Rappoport"	Kemerovo		Russian Federation
12	Regional Goverment Budgetary Healthcare State "Kostroma Oncology Center"	Kostroma		Russian Federation	156005
13	State Budgetary Institution of Healthcare "Leningrad Regional Clinical Oncological Dispensary named after V.I. L.D. Romana"	Kuz'molovskiy		Russian Federation
14	"Russian Cancer Research Center named after N.N. Blokhin "of the Ministry of Health of the Russian Federation	Moscow		Russian Federation
15	Branch of Hadassah Medical LTD Limited Liability Company	Moscow		Russian Federation
16	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
17	Joint Stock Company "K31 City"	Moscow		Russian Federation
18	JSC "Medsi Group"	Moscow		Russian Federation
19	Moscow City Oncology Hospital No. 62	Moscow		Russian Federation
20	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
21	Nizhny Novgorod Region State Budgetary Healthcare Facility "Clinical Diagnostics Center"	Nizhny Novgorod		Russian Federation	603006
22	LLC "DobroMed"	Novosibirsk		Russian Federation
23	State Budgetary Healthcare Institution "Novosibirsk Regional Clinical Oncology Center" of the Novosibirsk Region	Novosibirsk		Russian Federation
24	Federal State Budgetary Institution "National Medical Research Center for Radiology" of the Ministry of Health of the Russian Federation	Obninsk		Russian Federation
25	Budgetary healthcare institution of the Omsk region "Clinical oncological dispensary"	Omsk		Russian Federation
26	JSC "Modern Medical Technologies"	Saint Petersburg		Russian Federation	190013
27	Saint-Petersburg Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)	Saint Petersburg		Russian Federation	197758
28	Federal State Budgetary Educational Institution of Higher Education "Saint Petersburg State University"	Saint Petersburg		Russian Federation
29	Limited Liability Company "American Medical Clinic"	Saint Petersburg		Russian Federation
30	Limited Liability Company "Oncological Research Center"	Saint Petersburg		Russian Federation
31	Limited Liability Company "Strategic Medical Systems"	Saint Petersburg		Russian Federation
32	N.N. Petrov National Medicine Research Center of oncology	Saint Petersburg		Russian Federation
33	Private Medical Institution Evromedservis	Saint Petersburg		Russian Federation
34	Federal State Educational Institution of Higher Professional Education "Mordovia State University N.P. Ogareva "	Saransk		Russian Federation
35	City Hospital #40, Kurortny district	St. Petersburg		Russian Federation
36	State Health Care Institution "Volgograd Regional Clinical Oncology Dispensary № 1"	Volgograd		Russian Federation

Sponsors and Collaborators

• Biocad

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Biocad
• ClinicalTrials.gov Identifier: NCT05751928
• Other Study ID Numbers: BCD-217-3
• First Posted: Mar 2, 2023
• Last Update Posted: Mar 2, 2023
• Last Verified: Feb 1, 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Biocad: PD-1; CTLA-4; prolgolimab; nurulimab; immunotherapy; checkpoint inhibitors; CPI; programm death; cytotoxic T-lymphocyte-associated protein; Neoadjuvant Melanoma; Adjuvant Melanoma
• Additional relevant MeSH terms: Melanoma

Study Results

No Results Posted as of Mar 2, 2023