Phase 1 Study of BCD-245 in Subjects With Neuroblastoma
- Conditions
- Neuroblastoma
- Interventions
- Biological: BCD-245
- Registration Number
- NCT05782959
- Lead Sponsor
- Biocad
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 24
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 2 BCD-245 BCD-245 (anti-GD-2 monoclonal antibody), dose 2 Cohort 1 BCD-245 BCD-245 (anti-GD-2 monoclonal antibody), dose 1 Cohort 3 BCD-245 BCD-245 (anti-GD-2 monoclonal antibody), dose 3 Cohort 4 BCD-245 BCD-245 (anti-GD-2 monoclonal antibody), dose 4
- Primary Outcome Measures
Name Time Method Proportion of subjects with serious adverse reactions 52 weeks Proportion of subjects with 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
Name Time Method Proportion of subjects with anti-BCD-245 BAbs and NAbs 52 weeks 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) up to 4 weeks Half-life is the time taken to decrease the plasma concentration of a drug to one-half its original value
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
Trial Locations
- Locations (3)
Russian Cancer Research Center named after N.N. Blokhin "of the Ministry of Health of the Russian Federation
🇷🇺Moscow, Russian Federation
Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Immunology
🇷🇺Moscow, Russian Federation
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation
🇷🇺Saint Petersburg, Russian Federation