Clinical trial NCT03913923: 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
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Melanoma
Melanoma Metastatic
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2019-04-12
Enrollment: 117
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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Median Progression-Free Survival
timeFrame: 2 years
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 2 years
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Overall Response Rate
timeFrame: 2 years
measure: Disease Control Rate
timeFrame: 2 years
measure: Time to Response (TTR)
timeFrame: 2 years
measure: Duration of Response
timeFrame: 2 years
Other outcomes:
Locations:
city: The Settlement Of Lesnoy
country: Belarus
facility: State Institution "N.N. Aleksandrov Republican Research and Practical Center for Oncology and Medical Radiology"
state: Minsk District
city: Minsk
country: Belarus
facility: Healthcare Institution "Minsk Municipal Clinical Oncolo-gy Dispensary" (MMCOD)
city: Sochi
country: Russian Federation
facility: Clinical Oncologic Dispensary No. 2
state: Krasnodar Territory
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Regional Clinical Oncological Dispensary named after A.I. Kryzhanovsky
state: Krasnoyarsk Krai
city: Murmansk
country: Russian Federation
facility: Murmansk Regional Clinical Hospital named after P.A. Bayandina
state: Murmansk Oblast
city: Pyatigorsk
country: Russian Federation
facility: LLC "New Clinic"
state: Stavropol Krai
city: Yaroslavl
country: Russian Federation
facility: Regional Clinical Oncology Hospital
state: Yaroslavskaya Oblast
city: Arkhangel'sk
country: Russian Federation
facility: State Budgetary Healthcare Institution of the Ar-khangelsk Region "Arkhangelsk Clinical Oncology Dispensary"
city: Barnaul
country: Russian Federation
facility: Territorial State Budgetary Healthcare Institution "Altai Territorial Clinical Oncology Dispensary"
city: Chelyabinsk
country: Russian Federation
facility: State Budgetary Healthcare Institution "Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine",
city: Kazan
country: Russian Federation
facility: State public health institution "Republican Clinical Oncology Dispensary" of the Ministry of Health of the Republic of Tatarstan
city: Kostroma
country: Russian Federation
facility: Regional State Budgetary of Healthcare Insti-tution "Kostroma Oncology Dispensary"
city: Moscow
country: Russian Federation
facility: Medsi Group of Companies Joint-Stock Company
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: State Health Care Institution "Moscow City Oncology Hospital № 62" Moscow Health Department
city: Novosibirsk
country: Russian Federation
facility: State Budgetary Healthcare Institution of the Novosi-birsk Region "Novosibirsk Regional Clinical Oncolo-gy Dispensary"
city: Omsk
country: Russian Federation
facility: State budget healthcare institution Omsk region "Clinical Oncology Dispensary"
city: Saint Petersburg
country: Russian Federation
facility: JSC "Modern Medical Technologies"
city: Saint Petersburg
country: Russian Federation
facility: AV Medical Group Limited Liability Company
city: Saint Petersburg
country: Russian Federation
facility: Federal State Institution "N.N. Petrov National Medical Research Center for Oncology"
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 "St. Petersburg State University"
city: Samara
country: Russian Federation
facility: State-financed Health Institution "Samara Region Clinical Oncology Dispansary"
Study officials:
affiliation: Director of Clinical Development Department, BIOCAD
name: Arina V Zinkina-Orikhan, PhD
role: STUDY_DIRECTOR
References: