A Clinical Study of the Pharmacokinetics and Safety of BCD-263 and Opdivo® as Monotherapy in Subjects With Advanced Melanoma of the Skin

Study Overview
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Brief Summary
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The aim of the study BCD-263-1 is to prove the comparability of the pharmacokinetics and similarity of the safety, immunogenicity and pharmacodynamic profiles of BCD-263 and Opdivo following intravenous administration to subjects with advanced unresectable or metastatic melanoma of the skin. The study will have randomized, double-blind design with parallel assignment.

Detailed Description
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Following screening, subjects will be randomized to receive either BCD-263 or Opdivo in a 1:1 ratio and enter the main study period. During the main study period, subjects will receive therapy with BCD-263 or Opdivo, which will be administered intravenously until disease progression or signs of unacceptable toxicity develop (whichever occurs earlier). At Week 25, after completion of all scheduled procedures subjects in both groups will continue to receive open-label BCD-263 for up to a total of 2 years of therapy, or disease progression, or signs of unacceptable toxicity (whichever occurs first). Following discontinuation of the study therapy, the subjects will enter a follow-up period, during which data on overall survival will be collected through telephone contacts.

Official Title
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A Double-Blind, Randomized Clinical Study of the Pharmacokinetics and Safety of BCD-263 and Opdivo® as Monotherapy in Subjects With Advanced Melanoma of the Skin

Conditions
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Advanced Melanoma

Intervention / Treatment
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* Drug: BCD-263
* Drug: Opdivo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years at the time of signing the informed consent form; Body weight 60 to 90 kg. Histologically confirmed melanoma with the following prognostic characteristics: LDH <ULN of local laboratory (enrollment of subjects with LDH <2x ULN of local laboratory is allowed until the number of subjects with LDH >ULN is 30% of the total population of randomized subjects. The Sponsor will inform when enrollment of subjects is limited by LDH level <ULN of the local laboratory). Absence, according to the Investigator, of clinically significant symptoms associated with the tumor. Absence, according to the Investigator, of rapidly progressing metastatic melanoma. Newly diagnosed advanced unresectable (stage III) or metastatic disease (stage IV), or progressive disease during / relapsing after radical treatment. Exclusion Criteria: Indications for radical treatment (surgery, radiation therapy). Uveal or mucosal melanoma. Previous systemic anticancer therapy for advanced unresectable or metastatic skin melanoma (a history of neoadjuvant or adjuvant therapy is allowed, provided that the therapy was completed at least 12 weeks before randomization). Active CNS metastases and/or carcinomatous meningitis. Previous invasive cancer, excluding diseases treated with potentially curative therapy with no evidence of recurrence for 2 years from the start of this therapy (subjects with radically resected basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, cervical carcinoma in situ of the uterus and other carcinomas in situ may be included). Subjects with severe concomitant disorders, 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 and during the screening period. Concomitant diseases and/or conditions that significantly increase the risk of adverse events (AEs) during the study.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCD-263<br> | Drug: BCD-263<br>* BCD-263 at a dose 480 mg administered intravenously every 4 weeks up to 6 cycles<br>* Other names: Nivolumab;|
| Active Comparator: Opdivo<br> | Drug: Opdivo<br>* Opdivo at a dose 480 mg administered intravenously every 4 weeks up to 6 cycles<br>* Other names: Nivolumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-672) of nivolumab | To compare area under the drug concentration-time curve in the time interval from 0 to 672 hours after intravenous administration of BCD-263 and Opdivo | pre-dose to week 25 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | To compare the maximum concentration of nivolumab after intravenous administration of BCD-263 and Opdivo | week 25 | 
| AUC(0-∞) | To compare area under the drug concentration-time curve in the time interval from 0 to ∞ after intravenous administration of BCD-263 and Opdivo | week 25 | 
| Tmax | To compare time to the maximum concentration of nivolumab after intravenous administration of BCD-263 and Opdivo | week 25 | 
| T½ | To compare half-life period of nivolumab after intravenous administration of BCD-263 and Opdivo | week 25 | 
| Kel | To compare elimination rate constant of nivolumab after intravenous administration of BCD-263 and Opdivo | week 25 | 
| Vd | To compare steady-state volume of distribution of nivolumab after intravenous administration of BCD-263 and Opdivo | week 25 | 
| Cl | To compare total clearance of nivolumab after intravenous administration of BCD-263 and Opdivo | week 25 | 
| Ceoi | To compare plasma concentration at the and of infusion of nivolumab after intravenous administration of BCD-263 and Opdivo | week 25 | 
| Ctrough | To compare trough concentration at the and of infusion of nivolumab after intravenous administration of BCD-263 and Opdivo | week 25 | 
| Safety assessment | The subjects will undergo the vital sign assessment, physical and instrumental examination, sampling for complete blood count, blood chemistry, thyroid hormone tests, and urinalysis, as well as assessment of the presence and characteristics of adverse events to assess the safety of the investigational product | week 25 | 
| Immunogenicity assessment | Proportion of subjects with binding and/or neutralizing antibodies to nivolumab | week 25 | 
| Pharmacodynamics assessment | Occupancy of PD-1 receptors on CD4+ and CD8+ peripheral blood lymphocytes | week 25 | 
| Efficacy assessment: ORR | To compare overall response rate according to RECIST 1.1 and iRECIST criteria after administration of BCD-263 or Opdivo | week 25 | 
| Efficacy assessment: PFS | To compare progression-free survival according to RECIST 1.1 and iRECIST criteria after administration of BCD-263 or Opdivo | week 25 | 
| Efficacy assessment: overall survival | To compare overall survival according to RECIST 1.1 and iRECIST criteria after administration of BCD-263 or Opdivo | week 25 | 
| Efficacy assessment: DCR | To compare disease control rate according to RECIST 1.1 and iRECIST criteria after administration of BCD-263 or Opdivo | week 25 | 
| Efficacy assessment: time to response | To compare time to response according to RECIST 1.1 and iRECIST criteria after administration of BCD-263 or Opdivo | week 25 | 
| Efficacy assessment: duration of response | To compare duration of response according to RECIST 1.1 and iRECIST criteria after administration of BCD-263 or Opdivo | week 25 |