Clinical trial NCT05782959: Phase 1 Study of BCD-245 in Subjects With Neuroblastoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Neuroblastoma
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2023-03-24
Enrollment: 24
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Proportion of subjects with adverse reactions
timeFrame: 52 weeks
measure: Proportion of subjects with serious adverse reactions
timeFrame: 52 weeks
measure: Proportion of subjects with adverse reactions of grade 3 or higher according to CTCAE 5.0
timeFrame: 52 weeks
measure: Proportion of therapy discontinuations due to adverse reactions
timeFrame: up to 4 weeks
Secondary outcomes:
measure: Area under the plasma concentration versus time curve from time zero to t (AUC 0-t)
timeFrame: up to 4 weeks
measure: Area under the plasma concentration versus time curve from zero to time infinity (AUC 0-∞)
timeFrame: up to 4 weeks
measure: Peak plasma concentration (Cmax)
timeFrame: up to 4 weeks
measure: Time of peak plasma concentration (Tmax)
timeFrame: up to 4 weeks
measure: Half-life (T1/2)
timeFrame: up to 4 weeks
measure: Volume of distribution (Vd)
timeFrame: up to 4 weeks
measure: Mean steady-state peak plasma concentration (Cmax)
timeFrame: 20 weeks
measure: Pre-dose trough concentration (Ctrough)
timeFrame: 20 weeks
measure: Counts of lymphocytes and CD56+CD16+ (cytokine-secreting and cytotoxic) NK cells
timeFrame: 52 weeks
measure: Whole blood cytolytic activity test
timeFrame: 52 weeks
measure: Proportion of subjects with anti-BCD-245 BAbs and NAbs
timeFrame: 52 weeks
Other outcomes:
measure: Overall response rate
timeFrame: 52 weeks
measure: Duration of response
timeFrame: 52 weeks
measure: Time to response
timeFrame: 52 weeks
measure: Event-free survival
timeFrame: 52 weeks
measure: Overall survival
timeFrame: 52 weeks
Locations:
city: Moscow
country: Russian Federation
facility: Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Immunology
city: Moscow
country: Russian Federation
facility: Russian Cancer Research Center named after N.N. Blokhin "of the Ministry of Health of the Russian Federation
city: Saint Petersburg
country: Russian Federation
facility: Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation
Study officials:
References: