Clinical Study of the Efficacy and Safety of BCD-201 and Keytruda in Subjects With Advanced Melanoma

Study Overview
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Brief Summary
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This clinical study is designed as a randomized, double-blind trial. Subjects with unresectable, metastatic, or recurrent skin melanoma will be randomized to one of the two study groups (BCD-201 group and Keytruda group) at a 1:1 ratio. The goal of this study is to compare the efficacy and safety of BCD-201 and Keytruda as first-line therapy in subjects with unresectable, metastatic, or recurrent skin melanoma.

Official Title
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A Randomized, Double-Blind Clinical Study of the Efficacy and Safety of BCD-201 (JSC BIOCAD) and Keytruda® in Patients With Unresectable or Metastatic Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Drug: BCD-201
* Drug: Keytruda


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent; Histologically confirmed melanoma; Tumor first detected at the stage of advanced unresectable or metastatic disease, or disease progressing during or recurring after previous radical therapy; ECOG score 0-1; At least one measurable lesion according to RECIST 1.1; Laboratory test results consistent with adequate functioning of systems and organs; Willingness of men and women of childbearing potential to use highly effective contraceptive methods from the signing of the informed consent form, throughout the study and for 6 months after the administration of the last product dose. Exclusion Criteria: Indications for radical therapy (surgery, radiation therapy); Uveal, ocular or mucosal melanoma; Active CNS metastases and/or carcinomatous meningitis; Subjects with severe concomitant disorders, life-threatening acute complications of the primary disease; Concomitant diseases and/or conditions that significantly increase the risk of AEs during the study; Active, known or suspected autoimmune disorders (subjects with type 1 diabetes mellitus or hypothyroidism requiring only hormone-replacement therapy and those with skin disorders [vitiligo, alopecia, or psoriasis] not requiring systemic therapy are eligible to participate); The need for therapy with glucocorticoids or any other drugs with immunosuppressive effects within 14 days prior to randomization; History of (non-infectious) pneumonitis requiring glucocorticoid therapy or pneumonitis at the time of screening; Hypersensitivity or allergy to any of the pembrolizumab product components; Pregnancy or breastfeeding, as well as intention to become pregnant or father a child during the study period.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCD-201 group<br>BCD-201 200 mg as a 30-minute intravenous infusion once every 3 weeks | Drug: BCD-201<br>* up to 8 treatment cycles<br>* Other names: Pembrolizumab;|
| Active Comparator: Keytruda<br>Keytruda 200 mg as a 30-minute intravenous infusion once every 3 weeks | Drug: Keytruda<br>* up to 8 treatment cycles<br>* Other names: pembrolizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the overall response rate (ORR) in the BCD-201 group and the Keytruda group | ORR according to RECIST 1.1 | 24 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the ORR according to iRECIST in the BCD-201 group and the Keytruda group | ORR according to iRECIST | every 12 weeks up to 2 years | 
| To compare the duration of response in the BCD-201 group and the Keytruda group | Duration of response will be calculated from the moment of registration of response till event (progression or death) | up to 2 years | 
| To compare the time to response according to RECIST 1.1 and iRECIST in the BCD-201 group and the Keytruda group | time to response will be calculated from the randomization date | every 12 weeks up to 2 years | 
| To compare the disease control rate in the BCD-201 group and the Keytruda group | The percentage of the participants who have a Complete Response, a Partial Response or a Stable DIsease | up to 2 years | 
| To compare the progression-free survival (PFS) per RECIST 1.1 and iRECIST in the BCD-201 group and the Keytruda group | The time from the date of randomization until progression of disease according to RECIST 1.1 / iRECIST criteria or death | up to 2 years | 
| To compare the overall survival in the BCD-201 group and the Keytruda group | The time from the date of randomization until death | up to 2 years | 
| To compare the incidence of Treatment-Emergent Adverse Events (Safety profiles of BCD-201 and Keytruda) | Presence of any adverse events (AEs), presence of adverse reactions (ARs), presence of serious adverse reactions (SARs), presence of severe ARs (grade 3 or higher severity according to CTCAE v.5.0), presence of ARs leading to discontinuation of study therapy, presence of immune-mediated AEs | through study completion, an average of 2 years. | 
| Area under the concentration-time curve (AUC(0-504)) | Area under the plasma concentration versus time curve in the time interval from 0 to 504 hours | up to 24 weeks of the double-blind treatment period | 
| AUC(0-∞) | Area under the plasma concentration versus time curve in the time interval from 0 to time infinity | up to 24 weeks of the double-blind treatment period | 
| Peak Plasma Concentration (Cmax) | maximum concentration of pembrolizumab | up to 24 weeks of the double-blind treatment period | 
| Time to maximum concentration (Tmax) | time to maximum concentration of pembrolizumab | up to 24 weeks of the double-blind treatment period | 
| Elimination rate constant (kel) | kel of pembrolizumab | up to 24 weeks of the double-blind treatment period | 
| Total clearance (Cl) | Cl of pembrolizumab | up to 24 weeks of the double-blind treatment period | 
| Steady-state volume of distribution of the drug substance (Vd) | Vd of pembrolizumab | up to 24 weeks of the double-blind treatment period | 
| Half-life period (T1/2) | T1/2 of pembrolizumab | up to 24 weeks of the double-blind treatment period | 
| Concentrations at the end of each infusion (CEOI) | concentrations at the end of each infusion of pembrolizumab | up to 24 weeks of the double-blind treatment period | 
| To compare the immunogenicity of BCD-201 and Keytruda. | Development of binding and neutralizing antibodies to pembrolizumab | pre-dose to day169 of the double-blind treatment period, 8 timepoints |