Advanced Melanoma
Conditions
Brief 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.
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.
Interventions
Sponsors
Biocad
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-672) of nivolumab | pre-dose to week 25 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-∞) | week 25 | To compare area under the drug concentration-time curve in the time interval from 0 to ∞ after intravenous administration of BCD-263 and Opdivo |
| Tmax | week 25 | To compare time to the maximum concentration of nivolumab after intravenous administration of BCD-263 and Opdivo |
| T½ | week 25 | To compare half-life period of nivolumab after intravenous administration of BCD-263 and Opdivo |
| Kel | week 25 | To compare elimination rate constant of nivolumab after intravenous administration of BCD-263 and Opdivo |
| Vd | week 25 | To compare steady-state volume of distribution of nivolumab after intravenous administration of BCD-263 and Opdivo |
| Cl | week 25 | To compare total clearance of nivolumab after intravenous administration of BCD-263 and Opdivo |
| Ceoi | week 25 | To compare plasma concentration at the and of infusion of nivolumab after intravenous administration of BCD-263 and Opdivo |
| Ctrough | week 25 | To compare trough concentration at the and of infusion of nivolumab after intravenous administration of BCD-263 and Opdivo |
| Cmax | week 25 | To compare the maximum concentration of nivolumab after intravenous administration of BCD-263 and Opdivo |
| Immunogenicity assessment | week 25 | Proportion of subjects with binding and/or neutralizing antibodies to nivolumab |
| Pharmacodynamics assessment | week 25 | Occupancy of PD-1 receptors on CD4+ and CD8+ peripheral blood lymphocytes |
| Efficacy assessment: ORR | week 25 | To compare overall response rate according to RECIST 1.1 and iRECIST criteria after administration of BCD-263 or Opdivo |
| Efficacy assessment: PFS | week 25 | To compare progression-free survival according to RECIST 1.1 and iRECIST criteria after administration of BCD-263 or Opdivo |
| Efficacy assessment: overall survival | week 25 | To compare overall survival according to RECIST 1.1 and iRECIST criteria after administration of BCD-263 or Opdivo |
| Efficacy assessment: DCR | week 25 | To compare disease control rate according to RECIST 1.1 and iRECIST criteria after administration of BCD-263 or Opdivo |
| Efficacy assessment: time to response | week 25 | To compare time to response according to RECIST 1.1 and iRECIST criteria after administration of BCD-263 or Opdivo |
| Efficacy assessment: duration of response | week 25 | To compare duration of response according to RECIST 1.1 and iRECIST criteria after administration of BCD-263 or Opdivo |
| Safety assessment | week 25 | 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 |
Countries
Belarus, Russia
Outcome results
None listed