Clinical Study of the Efficacy and Safety of BCD-263 and Opdivo® as Monotherapy in Subjects With Advanced Melanoma of the Skin (UNIVERSE)

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

The aim of the study BCD-263-2/UNIVERSE is to demonstrate comparable efficacy and similar safety and immunogenicity profile of BCD-263 and Opdivo after repeated intravenous doses in subjects with advanced unresectable or metastatic melanoma of the skin.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma (Skin); 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): 392
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Brest, Belarus
    • Healthcare Institution "Brest Regional Oncological Dispensary"
  • Gomel, Belarus
    • Health Institution "Gomel Regional Clinical Oncology Center"
  • 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"
• Pakistan
  • Islamabad, Pakistan
    • Shaheed Zulfiqar Ali Bhutto Medical University
  • Peshawar, Pakistan
    • Rehman Medical Institute
• 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"
  • Ekaterinburg, Russian Federation
    • Sverdlovsk Regional Oncology Center
  • Ivanovo, Russian Federation, 153013
    • Ivanovo Regional Oncology Center
  • Izhevsk, Russian Federation, 426009
    • State Health Care Institution "Republican Clinical Cancer Center," the Ministry of Health of the Udmurt Republic
  • Kaliningrad, Russian Federation
    • State Budgetary Health Institution "Regional Clinical Hospital of Kaliningrad Region"
  • 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"
  • 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
    • State Budgetary Institution of Healthcare of the City of Moscow "Moscow Multidisciplinary Clinical Center "Kommunarka" 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
    • State Budgetary Healthcare Institution "Novosibirsk Regional Clinical Oncology Center" of the Novosibirsk Region
  • Omsk, Russian Federation
    • State budget healthcare institution Omsk region "Clinical Oncology Dispensary"
  • Perm, Russian Federation, 614066
    • Perm Region Oncology Dispensary
  • Perm, Russian Federation
    • State Budgetary Healthcare Institution of Perm Krai "Order of Honour" Perm Regional Clinical Hospital "
  • Rostov-on-Don, Russian Federation, 314019
    • Federal Government Budgetary Institution "National Institute of Cancer Research" of Ministry of Health of Russian Federation
  • Saint Petersburg, Russian Federation, 190013
    • JSC "Modern medical technologies"
  • Saint Petersburg, Russian Federation, 197758
    • Saint-Petersburg Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)
  • 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
    • JSC "North-West Centre of Evidence-Based Mediccine"
  • 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 "
  • Smolensk, Russian Federation, 214000
    • Provincial health official body "Smolensk Regional Clinical Oncological Dispensary"
  • Tomsk, Russian Federation
    • Federal State Budgetary Educational Institution of Higher Education "Siberian State Medical University" of the Ministry of Health of the Russian Federation
  • Tver, Russian Federation
    • Federal State Budgetary Institution of Health "Tver Regional Clinical Oncological Dispensary" of the Tver Region
  • Tyumen, Russian Federation
    • State Autonomus Institution of Health "Mulitiprofile Clinical Medical Centre "Medical City""
  • 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
  • Krasnodar Kari
    • Krasnodar, Krasnodar Kari, Russian Federation, 350040
      • Clinical Oncologic Dispensary No. 1
  • Krasnoyarsk Krai
    • Krasnoyarsk, Krasnoyarsk Krai, Russian Federation, 660133
      • Krasnoyarsk Regional Clinical Oncological Dispensary named after A.I. Kryzhanovsky

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Signed informed consent and the subject's ability to comply with the protocol requirements.
2. Age ≥18 years at the time of signing the informed consent form.

3. Histologically confirmed melanoma with the following prognostic characteristics:

   • LDH <ULN of local laboratory (enrollment of subjects with LDH <2 x 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.
5. Presence of a tumor sample (archived or new biopsy) that is suitable for evaluation for PD L1 expression in the Investigator's opinion.
6. At least one measurable lesion as per RECIST 1.1 based on independent central review.
7. ECOG score 0-1.
8. Laboratory test results consistent with adequate functioning of systems and organs.

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.
4. Active CNS metastases and/or carcinomatous meningitis.
5. Previous invasive cancer, excluding diseases treated with potentially radical 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.
8. 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).
9. The need for systemic corticosteroids (at doses equivalent to >10 mg/day prednisolone) or any other immunosuppressive drugs within 14 days prior to randomization. The use of inhaled and topical corticosteroids is allowed.
10. History of (non-infectious) pneumonitis requiring corticosteroid therapy or pneumonitis at the time of screening.
11. Any anticancer therapy or major surgery within 28 days prior to randomization, or the subject's AE (other than alopecia) caused by anticancer therapy has not yet recovered to CTCAE grade 1 or has not completely resolved.
12. Concomitant use of drugs or medical devices studied in other clinical studies or their use within 28 days prior to randomization.
13. Infections requiring therapy or systemic antibiotics within 14 days prior to randomization.
14. Administration of a live and/or attenuated vaccine within 28 days prior to randomization.
15. Positive HIV-1 or HIV-2 test.
16. HBV/HCV infections (subjects with a negative PCR result for hepatitis C virus RNA, without significant abnormalities in blood chemistry tests, examined by an infectious disease specialist and not requiring specific antiviral treatment at the time of screening, may be included in the study. Subjects with a positive HbsAg test result cannot be included in the study).
17. Impossibility to administer intravenous contrast agents (including due to hypersensitivity to contrast media).
18. Hypersensitivity or allergy to any of the nivolumab product components. Hypersensitivity or allergy to medicinal products obtained based on Chinese hamster ovary cells, or history of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies or hybrid proteins.
19. Pregnancy or breastfeeding, as well as intention to become pregnant or father a child during the study period.

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; BCD-263 will be administered during main period and open-label period	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; Opdivo will be administered during main period	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
Overall response rate (ORR) according to RECIST 1.1	To compare the overall response rates (ORRs) after administration of BCD-263 and Opdivo in subjects with advanced unresectable or metastatic skin melanoma	Week 25

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
DCR	To compare disease control rate according to RECIST 1.1 and iRECIST criteria after administration of BCD-263 or Opdivo	week 25
PFS	To compare progression-free survival according to RECIST 1.1 and iRECIST criteria after administration of BCD-263 or Opdivo	week 25
Overall survival	To compare overall survival according to RECIST 1.1 and iRECIST criteria after administration of BCD-263 or 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	Through week 105
Immunogenicity assessment	Proportion of subjects with binding and/or neutralizing antibodies to nivolumab	Through week 105

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC(0-∞) (optional)	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
AUC(0-672) of nivolumab (optional)	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	week 25
Cmax (optional)	To compare the maximum concentration of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
Tmax (optional)	To compare time to the maximum concentration of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
T½ (optional)	To compare half-life period of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
Kel (optional)	To compare elimination rate constant of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
Vd (optional)	To compare steady-state volume of distribution of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
Cl (optional)	To compare total clearance of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
Ceoi (optional)	To compare plasma concentration at the and of infusion of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
Cmin (optional)	To compare minimal concentration of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
Cmax, ss (optional)	To compare steady-state maximum concentration of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
Ctrough, ss (optional)	To compare steady-state trough concentration of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
Ctrough (optional)	To compare trough concentration of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25

Collaborators and Investigators

• Sponsor: Biocad

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: October 11, 2024
• First Submitted That Met QC Criteria: October 11, 2024
• First Posted (Actual): October 15, 2024

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-263-2

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.: No