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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Melanoma
• Intervention / Treatment: Drug: BCD-263; Drug: Opdivo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belarus
  • Minsk, Belarus, 220013
    • Healthcare Institution "Minsk City Clinical Cancer Center"
  • Minsk, Belarus, 223040
    • State Institution "Republic Scientific and Practical Centre for Oncology and Medical Radiology Named after N.N.Aleksandrov"
• Russian Federation
  • Arkhangel'sk, Russian Federation, 164523
    • State Budgetary Institution of Healthcare of the Arkhangelsk Region "Severodvinsk City Hospital №2 of Emergency"
  • Barnaul, Russian Federation, 656045
    • Regional State Budgetary Healthcare Institution "Altai Regional Oncological Dispensary"
  • Kaliningrad, Russian Federation, 236016
    • Federal State Educational Institution of Higher Education "Baltic Federal University Named after Immanuel Kant"
  • Kaliningrad, Russian Federation, 236022
    • Limited Liability Company "Ars Medica Centre"
  • Kaluga, Russian Federation, 248007
    • State Budgetary Healthcare Institution of Kaluga Region "Kaluga Region Clinical Oncological Dispensary"
  • Kazan, Russian Federation
    • State Autonomous Health Institution "Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of Tatarstan named after Professor M.Z. Sigal"
  • Kostroma, Russian Federation, 156005
    • Regional State Budgetary of Healthcare Insti-tution "Kostroma Clinical Oncology Dispensary"
  • Moscow, Russian Federation
    • State Budgetary Healthcare Institution "Moscow Clinical Scientific Center funded by Moscow Health Department" (SBHI MCSC MHD)
  • Moscow, Russian Federation
    • JSC "Medsi Group"
  • Moscow, Russian Federation
    • Moscow City Oncology Hospital No. 62
  • Moscow, Russian Federation
    • 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, 115478
    • "Russian Cancer Research Center named after N.N. Blokhin "of the Ministry of Health of the Russian Federation
  • Nizhny Novgorod, Russian Federation, 603126
    • Nizhny Novgorod Region State Budgetary Healthcare Institution "Nizhny Novgorod Regional Clinical Oncological Dispensary"
  • Novosibirsk, Russian Federation, 630108
    • State Budgetary Healthcare Institution of Novosibirsk Region "Novosibirsk Region Clinical Oncological Dispensary"
  • Omsk, Russian Federation
    • State budget healthcare institution Omsk region "Clinical Oncology Dispensary"
  • Saint Petersburg, Russian Federation, 190013
    • JSC "Modern medical technologies"
  • Saint Petersburg, Russian Federation
    • "Saint Petersburg Clinical Research and Practice Center for Specialized Medical Care (Oncology)"
  • Saint Petersburg, Russian Federation
    • Private Medical Institution Evromedservis
  • Saint Petersburg, Russian Federation
    • Limited Liability Company "Oncological Research Center"
  • Saint Petersburg, Russian Federation, 195271
    • Private healthcare institution "Clinical hospital "RZD-Medicine" of the city of Saint Petersburg"
  • Saint-Petersburg, Russian Federation
    • Federal State Budgetary Institution "N.N. Petrov Research Institute of Oncology" of the Ministry of Healthcare of the Russian Federation
  • Samara, Russian Federation, 443031
    • State-financed Health Institution "Samara Region Clinical Oncology Dispensary"
  • Saransk, Russian Federation
    • Federal State Educational Institution of Higher Professional Education "Mordovia State University N.P. Ogareva "
  • Tomsk, Russian Federation, 634009
    • Limited Liability Company "Nebbiolo"
  • Ufa, Russian Federation, 450054
    • Republican Clinical Oncology Dispensary of Ministry of Health republic Bashkortostan
  • Volgograd, Russian Federation
    • State Health Care Institution "Volgograd Regional Clinical Oncology Dispensary № 1"
  • Chelyabinsk Oblast
    • Chelyabinsk, Chelyabinsk Oblast, Russian Federation, 454087
      • Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine
  • Stavropol Krai
    • Pyatigorsk, Stavropol Krai, Russian Federation, 357500
      • LLC "New Clinic"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years at the time of signing the informed consent form;
2. Body weight 60 to 90 kg.

3. 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.
4. Newly diagnosed advanced unresectable (stage III) or metastatic disease (stage IV), or progressive disease during / relapsing after radical treatment.

Exclusion Criteria:

1. Indications for radical treatment (surgery, radiation therapy).
2. Uveal or mucosal melanoma.
3. 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).
4. Active CNS metastases and/or carcinomatous meningitis.
5. 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).
6. 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.
7. Concomitant diseases and/or conditions that significantly increase the risk of adverse events (AEs) during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Biocad
• Investigators: Study Director: Arina V Zinkina-Orikhan, Director of Clinical Development Department, BIOCAD

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2023
• Primary Completion (Actual): January 31, 2024
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: October 27, 2023
• First Submitted That Met QC Criteria: October 27, 2023
• First Posted (Actual): November 2, 2023

Study Record Updates

• Last Update Posted (Estimated): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 3, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma, Cutaneous Malignant; Melanoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Nivolumab
• Other Study ID Numbers: BCD-263-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes