Phase 1 Study of BCD-245 in Subjects With Neuroblastoma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1 BCD-245 (anti-GD-2 monoclonal antibody), dose 1 |
Biological: BCD-245
BCD-245 is administered as prolonged intravenous infusions during each cycle
|
| Experimental: Cohort 2 BCD-245 (anti-GD-2 monoclonal antibody), dose 2 |
Biological: BCD-245
BCD-245 is administered as prolonged intravenous infusions during each cycle
|
| Experimental: Cohort 3 BCD-245 (anti-GD-2 monoclonal antibody), dose 3 |
Biological: BCD-245
BCD-245 is administered as prolonged intravenous infusions during each cycle
|
| Experimental: Cohort 4 BCD-245 (anti-GD-2 monoclonal antibody), dose 4 |
Biological: BCD-245
BCD-245 is administered as prolonged intravenous infusions during each cycle
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
- Proportion of subjects with anti-BCD-245 BAbs and NAbs [52 weeks]
Other Outcome Measures
- Overall response rate [52 weeks]
Includes complete response, very good partial response, partial response
- Duration of response [52 weeks]
- Time to response [52 weeks]
- Event-free survival [52 weeks]
- Overall survival [52 weeks]
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Immunology | Moscow | Russian Federation | ||
| 2 | Russian Cancer Research Center named after N.N. Blokhin "of the Ministry of Health of the Russian Federation | Moscow | Russian Federation | ||
| 3 | Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation | Saint Petersburg | Russian Federation |
Sponsors and Collaborators
- Biocad
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BCD-245-1