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.

Study Overview

• Status: Recruiting
• Conditions: Neuroblastoma
• Intervention / Treatment: Biological: BCD-245

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 Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Maria Morozova; Phone Number: 8436 +7 (495) 992 66 28; Email: morozovama@biocad.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Recruiting
    • Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology
    • Contact: Mikhail A Maschan; Phone Number: +7 495 287 65 70; Email: info@fnkc.ru
  • Moscow, Russian Federation
    • Recruiting
    • Russian Cancer Research Center named after N.N. Blokhin "of the Ministry of Health of the Russian Federation
    • Contact: Svetlana R Varfolomeev; Phone Number: +7 (499) 324-24-24; Email: info@ronc.ru
  • Saint Petersburg, Russian Federation
    • Recruiting
    • Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation
    • Contact: Ludmila S Zubarovskaya; Phone Number: +7(812) 338 6265; Email: bmt-director@1spbgmu.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to response		52 weeks
Overall survival		52 weeks
Overall response rate	Includes complete response, very good partial response, partial response	52 weeks
Duration of response		52 weeks
Event-free survival		52 weeks

Collaborators and Investigators

• Sponsor: Biocad

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2021
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: February 16, 2023
• First Submitted That Met QC Criteria: March 13, 2023
• First Posted (Actual): March 24, 2023

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Neuroblastoma
• Other Study ID Numbers: BCD-245-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No