Study of Efficacy and Safety of BCD-217 (Anti-CTLA-4 and Anti-PD-1) Followed By BCD-100 (Anti-PD-1) Versus BCD-100 Monotherapy as First-Line Treatment in Patients With Unresectable or Metastatic Melanoma

Melanoma Clinical Trial

— OBERTON  

Official title:

International Multicenter Double-Blind Placebo-Controlled Comparative Randomized Trial of Efficacy and Safety of BCD-217 (Anti-CTLA-4 and Anti-PD-1) And BCD-100 (Anti-PD-1) Therapy Compared to BCD-100 Monotherapy as First-Line Treatment in Patients With Unresectable or Metastatic Melanoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03913923
• Other study ID #: BCD-217-1
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 1, 2019
• Est. completion date: December 2023

Study information

• Verified date: February 2023
• Source: Biocad
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter randomized double-blind placebo-controlled phase II clinical trial. The purpose of this trial is to evaluate efficacy and safety of therapy consisting of BCD-217 (fixed dose combination of anti-CTLA-4 and anti-PD-1 monoclonal antibodies) and sequential BCD-100 (anti-PD-1 monoclonal antibody) versus BCD-100 monotherapy as first-line treatment in patients with treatment-naïve unresectable or metastatic melanoma.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 117
• Est. completion date: December 2023
• Est. primary completion date: July 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Signed Informed Consent Form and the subject's ability to follow the Protocol requirements;

2. Age: 18 years and older at the signing of the informed consent;

3. Histologically verified (documented) melanoma;

4. Previously untreated unresectable stage III melanoma or metastatic stage IV melanoma;

5. Available tissue blocks for histological examination or patient's agreement to give biopsy specimens

6. Patient's consent for PD-L1 expression status and BRAF V600 testing;

7. ECOG performance status of 0 or 1;

8. Life expectancy of at least 12 weeks from the screening;

9. At least one RECIST 1.1-defined measurable target lesion confirmed by an independent review;

10. Patients with reproductive potential must agree to practice acceptable methods of birth control throughout the entire trial period, starting from signing the informed consent and up to 24 weeks after the last dose of investigational drug.

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 patient 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 the patients 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 patients 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 patient'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 Metastatic

Intervention

Biological:
• BCD-217
Combination of anti-CTLA-4 and anti-PD-1 monoclonal antibodies, 1mg/kg and 3 mg/mg, respectively, given Q3W as IV infusion for first 4 blinded infusions
• BCD-100
Anti-PD-1 monoclonal antibody, 3 mg/kg, given Q3W as IV infusion for first 4 blinded infusions, after - 1 mg/kg, given Q2W as IV infusion

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
Belarus	Healthcare Institution "Minsk Municipal Clinical Oncolo-gy Dispensary" (MMCOD)	Minsk
Belarus	State Institution "N.N. Aleksandrov Republican Research and Practical Center for Oncology and Medical Radiology"	The Settlement Of Lesnoy	Minsk District
Russian Federation	State Budgetary Healthcare Institution of the Ar-khangelsk Region "Arkhangelsk Clinical Oncology Dispensary"	Arkhangel'sk
Russian Federation	Territorial State Budgetary Healthcare Institution "Altai Territorial Clinical Oncology Dispensary"	Barnaul
Russian Federation	State Budgetary Healthcare Institution "Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine",	Chelyabinsk
Russian Federation	State public health institution "Republican Clinical Oncology Dispensary" of the Ministry of Health of the Republic of Tatarstan	Kazan
Russian Federation	Regional State Budgetary of Healthcare Insti-tution "Kostroma Oncology Dispensary"	Kostroma
Russian Federation	Krasnoyarsk Regional Clinical Oncological Dispensary named after A.I. Kryzhanovsky	Krasnoyarsk	Krasnoyarsk Krai
Russian Federation	"Russian Cancer Research Center named after N.N. Blokhin "of the Ministry of Health of the Russian Federation	Moscow
Russian Federation	Medsi Group of Companies Joint-Stock Company	Moscow
Russian Federation	State Health Care Institution "Moscow City Oncology Hospital ? 62" Moscow Health Department	Moscow
Russian Federation	Murmansk Regional Clinical Hospital named after P.A. Bayandina	Murmansk	Murmansk Oblast
Russian Federation	State Budgetary Healthcare Institution of the Novosi-birsk Region "Novosibirsk Regional Clinical Oncolo-gy Dispensary"	Novosibirsk
Russian Federation	State budget healthcare institution Omsk region "Clinical Oncology Dispensary"	Omsk
Russian Federation	LLC "New Clinic"	Pyatigorsk	Stavropol Krai
Russian Federation	AV Medical Group Limited Liability Company	Saint Petersburg
Russian Federation	Federal State Budgetary Educational Institution of Higher Education "St. Petersburg State University"	Saint Petersburg
Russian Federation	Federal State Institution "N.N. Petrov National Medical Research Center for Oncology"	Saint Petersburg
Russian Federation	JSC "Modern Medical Technologies"	Saint Petersburg
Russian Federation	Saint-Petersburg Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)	Saint Petersburg
Russian Federation	State-financed Health Institution "Samara Region Clinical Oncology Dispansary"	Samara
Russian Federation	Clinical Oncologic Dispensary No. 2	Sochi	Krasnodar Territory
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	Median Progression-Free Survival		2 years
Secondary	Progression-Free Survival (PFS)	The time from the date of randomization until progression of disease per RECIST 1.1 and iRECIST or death	2 years
Secondary	Overall Survival (OS)	The time from the date of randomization until death	2 years
Secondary	Overall Response Rate	The percentage of the participants who have a Complete Response or a Partial Response as assessed by a blind independent central reviewer per RECIST 1.1. and iRECIST	2 years
Secondary	Disease Control Rate	The percentage of the participants who have a Complete Response, a Partial Response or a Stable DIsease as assessed by a blind independent central reviewer per RECIST 1.1. and iRECIST	2 years
Secondary	Time to Response (TTR)	TTR will be calculated from the randomization date	2 years
Secondary	Duration of Response	DOR will be calculated from the moment of registration of response till event (progression or death)	2 years