Phase 1 Study of BCD-245 in Subjects With Neuroblastoma

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

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.

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.

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