Evaluation of the Safety and Pharmacokinetics of Dinutuximab Beta As Maintenance Therapy in Chinese Participants With High-Risk Neuroblastoma

An Open-Label, Multi-Center, Single-Arm, Phase 1 Study Evaluating the Safety and Pharmacokinetics of Dinutuximab Beta as Maintenance Therapy in Chinese Patients With High-Risk Neuroblastoma

This was an open-label, multi-center, single-arm, Phase 1 study. The purpose of this study was for evaluating the safety and pharmacokinetics of dinutuximab beta as maintenance therapy in Chinese participants with high-risk neuroblastoma

Study Overview

• Status: Completed
• Conditions: High-risk Neuroblastoma
• Intervention / Treatment: Drug: Dinutuximab Beta; Drug: 13-cis-Retinoic Acid

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University Cancer Institute & Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The Children's Hospital Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

1. Signed informed consent form (ICF) and ability to comply with study requirements
2. Age ≥ 12 months at consent
3. Diagnosis of high-risk neuroblastoma according to the International Neuroblastoma Staging System (INSS) criteria.
4. Participants who have previously received induction chemotherapy and achieved a partial or complete response followed by myeloablative therapy and stem cell transplantation. Stem cell transplantation should be completed within 120 days of dinutuximab beta first administration

Exclusion Criteria:

1. Hypersensitivity to ≥ 1 component of dinutuximab beta antibody or against mouse proteins
2. Actively progressive disease (not stabilized) or recurrent disease at the time of inclusion into the study
3. Previous treatment with anti-GD2 antibody before enrolling in this study

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Dinutuximab Beta + 13-cis-Retinoic Acid; The study recruited participants who were hospitalized (with full resuscitation equipment) on Day 1 of each cycle and received continuous infusion of dinutuximab beta for 10 consecutive days in 35-day cycles. Participants could be discharged from the hospital at the investigator's discretion. Participants continued to receive 13-cis-retinoic acid orally for 14 days after completion of dinutuximab beta infusion (day 12-25 in each cycle).

Drug: Dinutuximab Beta; Dinutuximab beta was administered intravenously at a dosage of 10 milligrams/ meters squared (mg/m2) per day for 10 consecutive days; Drug: 13-cis-Retinoic Acid; 13-cis-Retinoic Acid was administered orally at a daily total dose of 160 mg/m2, divided into approximately two equal doses given twice daily for 14 days following the conclusion of dinutuximab beta infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	Number of participants with treatment-emergent adverse events (TEAEs) and serious treatment-emergent adverse event, characterized by type, frequency, severity (as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 [NCI-CTCAE v 5.0]), timing, seriousness, relationship to study treatment, and other safety assessments.	From the first dose of study drug(s) to 40 days after the last dose; up to approximately 1 year and 1 month
Area Under the Serum Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of Dinutuximab Beta		From Cycle 1 Day 1 pre-dose to Cycle 2 Day 1 pre-dose (Each cycle is 35 Days)
Area Under the Serum Concentration-time Curve From Zero to Infinity (AUC0-∞) of Dinutuximab Beta		From Cycle 1 Day 1 pre-dose to Cycle 2 Day 1 pre-dose (Each cycle is 35 Days)
Maximum Observed Serum Concentration (Cmax) of Dinutuximab Beta		From Cycle 1 Day 1 pre-dose to Cycle 2 Day 1 pre-dose (Each cycle is 35 Days)
Time to Maximum Serum Concentration (Tmax) of Dinutuximab Beta		From Cycle 1 Day 1 pre-dose to Cycle 2 Day 1 pre-dose (Each cycle is 35 Days)
Half-Life (t1/2) of Dinutuximab Beta		From Cycle 1 Day 1 pre-dose to Cycle 2 Day 1 pre-dose (Each cycle is 35 Days)
Clearance (CL) of Dinutuximab Beta		From Cycle 1 Day 1 pre-dose to Cycle 2 Day 1 pre-dose (Each cycle is 35 Days)
Volume of Distribution During Terminal Phase (Vz) of Dinutuximab Beta		From Cycle 1 Day 1 pre-dose to Cycle 2 Day 1 pre-dose (Each cycle is 35 Days)
Volume of Distribution at Steady State (Vss) of Dinutuximab Beta		From Cycle 1 Day 1 pre-dose to Cycle 2 Day 1 pre-dose (Each cycle is 35 Days)

Collaborators and Investigators

• Sponsor: BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2022
• Primary Completion (Actual): June 29, 2023
• Study Completion (Actual): June 29, 2023

Study Registration Dates

• First Submitted: April 11, 2022
• First Submitted That Met QC Criteria: May 10, 2022
• First Posted (Actual): May 13, 2022

Study Record Updates

• Last Update Posted (Actual): October 4, 2024
• Last Update Submitted That Met QC Criteria: June 20, 2024
• Last Verified: June 1, 2024

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; Antineoplastic Agents; Dermatologic Agents; Keratolytic Agents; Dinutuximab; Tretinoin; Isotretinoin
• Other Study ID Numbers: BGB-dinutuximab beta-101; CTR20221154 (Other Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No