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

Advanced Melanoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06112808
• Other study ID #: BCD-263-1
• Status: Recruiting
• Phase: Phase 1
• Start date: May 29, 2023
• Est. completion date: January 2027

Study information

• Verified date: November 2023
• Source: Biocad
• Contact: Anton Lutckii, MD PhD
• Phone: +7 (812) 380 49 33
• Email: lutskii[@]biocad.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: January 2027
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Melanoma
• Melanoma

Intervention

Drug:
• BCD-263
BCD-263 at a dose 480 mg administered intravenously every 4 weeks up to 6 cycles
• Opdivo
Opdivo at a dose 480 mg administered intravenously every 4 weeks up to 6 cycles

Locations

Country	Name	City	State
Belarus	Healthcare Institution "Minsk City Clinical Cancer Center"	Minsk
Belarus	State Institution "Republic Scientific and Practical Centre for Oncology and Medical Radiology Named after N.N.Aleksandrov"	Minsk
Russian Federation	State Budgetary Institution of Healthcare of the Arkhangelsk Region "Severodvinsk City Hospital ?2 of Emergency"	Arkhangel'sk
Russian Federation	Regional State Budgetary Healthcare Institution "Altai Regional Oncological Dispensary"	Barnaul
Russian Federation	Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine	Chelyabinsk	Chelyabinsk Oblast
Russian Federation	Federal State Educational Institution of Higher Education "Baltic Federal University Named after Immanuel Kant"	Kaliningrad
Russian Federation	Limited Liability Company "Ars Medica Centre"	Kaliningrad
Russian Federation	State Budgetary Healthcare Institution of Kaluga Region "Kaluga Region Clinical Oncological Dispensary"	Kaluga
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"	Kazan
Russian Federation	Regional State Budgetary of Healthcare Insti-tution "Kostroma Clinical Oncology Dispensary"	Kostroma
Russian Federation	"Russian Cancer Research Center named after N.N. Blokhin "of the Ministry of Health of the Russian Federation	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 Healthcare Institution "Moscow Clinical Scientific Center funded by Moscow Health Department" (SBHI MCSC MHD)	Moscow
Russian Federation	Nizhny Novgorod Region State Budgetary Healthcare Institution "Nizhny Novgorod Regional Clinical Oncological Dispensary"	Nizhny Novgorod
Russian Federation	State Budgetary Healthcare Institution of Novosibirsk Region "Novosibirsk Region Clinical Oncological Dispensary"	Novosibirsk
Russian Federation	State budget healthcare institution Omsk region "Clinical Oncology Dispensary"	Omsk
Russian Federation	LLC "New Clinic"	Pyatigorsk	Stavropol Krai
Russian Federation	"Saint Petersburg Clinical Research and Practice Center for Specialized Medical Care (Oncology)"	Saint Petersburg
Russian Federation	JSC "Modern Medical Technologies"	Saint Petersburg
Russian Federation	Limited Liability Company "Oncological Research Center"	Saint Petersburg
Russian Federation	Private healthcare institution "Clinical hospital "RZD-Medicine" of the city of Saint Petersburg"	Saint Petersburg
Russian Federation	Private Medical Institution Evromedservis	Saint Petersburg
Russian Federation	Federal State Budgetary Institution "N.N. Petrov Research Institute of Oncology" of the Ministry of Healthcare of the Russian Federation	Saint-Petersburg
Russian Federation	State-financed Health Institution "Samara Region Clinical Oncology Dispensary"	Samara
Russian Federation	Federal State Educational Institution of Higher Professional Education "Mordovia State University N.P. Ogareva "	Saransk
Russian Federation	Limited Liability Company "Nebbiolo"	Tomsk
Russian Federation	Republican Clinical Oncology Dispensary of Ministry of Health republic Bashkortostan	Ufa
Russian Federation	State Health Care Institution "Volgograd Regional Clinical Oncology Dispensary ? 1"	Volgograd

Sponsors (1)

Lead Sponsor	Collaborator
Biocad

Countries where clinical trial is conducted

Belarus,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Cmax	To compare the maximum concentration of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
Secondary	AUC(0-8)	To compare area under the drug concentration-time curve in the time interval from 0 to 8 after intravenous administration of BCD-263 and Opdivo	week 25
Secondary	Tmax	To compare time to the maximum concentration of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
Secondary	T½	To compare half-life period of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
Secondary	Kel	To compare elimination rate constant of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
Secondary	Vd	To compare steady-state volume of distribution of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
Secondary	Cl	To compare total clearance of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
Secondary	Ceoi	To compare plasma concentration at the and of infusion of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
Secondary	Ctrough	To compare trough concentration at the and of infusion of nivolumab after intravenous administration of BCD-263 and Opdivo	week 25
Secondary	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
Secondary	Immunogenicity assessment	Proportion of subjects with binding and/or neutralizing antibodies to nivolumab	week 25
Secondary	Pharmacodynamics assessment	Occupancy of PD-1 receptors on CD4+ and CD8+ peripheral blood lymphocytes	week 25
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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