Phase 1 Study of BCD-245 in Subjects With Neuroblastoma

Study Overview
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Brief Summary
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The aim of the study is to investigate the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of BCD-245 after its single and multiple intravenous infusions at escalating doses in subjects with relapsed/refractory neuroblastoma.

Detailed Description
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The study includes 2 stages: 1) Data collection and safety analysis for the first four subjects 12 years of age and older from Cohort 1 2) Data collection and analysis of safety, pharmacokinetics, pharmacodynamics and immunogenicity in all cohorts (Cohorts 1-4). The design of this Phase I study is based on standard 3 + 3 design approaches. Cohort 1 includes 4 subjects aged 12 years old and older, and 2 subjects aged 3 years old and older. Cohorts 2-4 include 3-6 subjects aged 3 years and older.

Official Title
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An Open-Label, Dose-Escalation, Non-comparative Clinical Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of BCD-245 (JSC BIOCAD, Russia) Administered Intravenously to Subjects With Neuroblastoma

Conditions
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Neuroblastoma

Intervention / Treatment
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* Biological: BCD-245


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 3 years and older (12 years and older for the first four subjects) at the time of signing the informed consent form Established diagnosis of neuroblastoma (confirmed by the study site laboratory where the subject will be treated) based on: a) histological examination of the tumor tissue (with or without immunohistochemistry) or b) presence of typical tumor agglomerates in the bone marrow and/or meta-iodobenzylguanidine-accumulating focus (foci) and an increase in the level of catecholamine metabolites in serum and/or urine Relapsed or refractory neuroblastoma resistant to the anti-relapse therapy adopted at the study site Satisfactory performance status (>70 on the Lansky or Karnofsky scale) Life expectancy >8 weeks Exclusion Criteria: Indications for radiation therapy, surgical intervention for the primary disease at screening Isolated CNS relapse of neuroblastoma Planned use of any anticancer drugs concomitantly with BCD-245 in this clinical trial The need for continuous use of anticonvulsants Clinically significant neurological deficit or grade >2 peripheral neuropathy (CTCAE 5.0) The need or probable need for systemic continuous use of glucocorticosteroids or other immunosuppressive drugs Signs of respiratory distress (dyspnea at rest and oxygen saturation <94% without oxygen supplementation) Any severe organ dysfunction (> CTCAE 5.0 severity grade 2) at screening, except for hematological abnormalities. Body weight less than 10 kg. Subject receiving anti-GD2 monoclonal antibody therapy within 6 weeks or less prior to intended study drug infusion

Ages Eligible for Study
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Minimum Age: 3 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>BCD-245 (anti-GD-2 monoclonal antibody), dose 1 | Biological: BCD-245<br>* BCD-245 is administered as prolonged intravenous infusions during each cycle<br>|
| Experimental: Cohort 2<br>BCD-245 (anti-GD-2 monoclonal antibody), dose 2 | Biological: BCD-245<br>* BCD-245 is administered as prolonged intravenous infusions during each cycle<br>|
| Experimental: Cohort 3<br>BCD-245 (anti-GD-2 monoclonal antibody), dose 3 | Biological: BCD-245<br>* BCD-245 is administered as prolonged intravenous infusions during each cycle<br>|
| Experimental: Cohort 4<br>BCD-245 (anti-GD-2 monoclonal antibody), dose 4 | Biological: BCD-245<br>* BCD-245 is administered as prolonged intravenous infusions during each cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with adverse reactions |  | 52 weeks | 
| Proportion of subjects with serious adverse reactions |  | 52 weeks | 
| Proportion of subjects with adverse reactions of grade 3 or higher according to CTCAE 5.0 |  | 52 weeks | 
| Proportion of therapy discontinuations due to adverse reactions |  | up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve from time zero to t (AUC 0-t) |  | up to 4 weeks | 
| Area under the plasma concentration versus time curve from zero to time infinity (AUC 0-∞) |  | up to 4 weeks | 
| Peak plasma concentration (Cmax) |  | up to 4 weeks | 
| Time of peak plasma concentration (Tmax) |  | up to 4 weeks | 
| Half-life (T1/2) | Half-life is the time taken to decrease the plasma concentration of a drug to one-half its original value | up to 4 weeks | 
| Volume of distribution (Vd) |  | up to 4 weeks | 
| Mean steady-state peak plasma concentration (Cmax) |  | 20 weeks | 
| Pre-dose trough concentration (Ctrough) |  | 20 weeks | 
| Counts of lymphocytes and CD56+CD16+ (cytokine-secreting and cytotoxic) NK cells |  | 52 weeks | 
| Whole blood cytolytic activity test |  | 52 weeks | 
| Proportion of subjects with anti-BCD-245 BAbs and NAbs |  | 52 weeks |