High-risk Neuroblastoma
Conditions
Brief summary
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
Interventions
DRUGDinutuximab Beta
Dinutuximab beta was administered intravenously at a dosage of 10 milligrams/ meters squared (mg/m2) per day for 10 consecutive days
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.
Sponsors
BeiGene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Months to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | From the first dose of study drug(s) to 40 days after the last dose; up to approximately 1 year and 1 month | 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. |
| 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) | — |
Countries
China
Participant flow
Recruitment details
Participants were enrolled in three study centers across China. The study was conducted from June 7th, 2022, and completed on June 29, 2023.
Participants by arm
| Arm | Count |
|---|---|
| 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).
Dinutuximab Beta: Dinutuximab beta was administered intravenously at a dosage of 10 milligrams/ meters squared (mg/m2/day) for 10 consecutive days
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. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Dinutuximab Beta + 13-cis-Retinoic Acid | — |
|---|---|---|
| Age, Continuous | 5.0 years STANDARD_DEVIATION 1.41 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 2 Participants | — |
| Sex: Female, Male Male | 6 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 1 / 8 |
Outcome results
Primary
Area Under the Serum Concentration-time Curve From Zero to Infinity (AUC0-∞) of Dinutuximab Beta
Time frame: From Cycle 1 Day 1 pre-dose to Cycle 2 Day 1 pre-dose (Each cycle is 35 Days)
Population: Pharmacokinetic (PK) Analysis Set was defined as participants who had at least 1 available postbaseline PK data in the Safety Analysis Set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dinutuximab Beta + 13-cis-Retinoic Acid | Area Under the Serum Concentration-time Curve From Zero to Infinity (AUC0-∞) of Dinutuximab Beta | 4228.6 h*ug/mL | Geometric Coefficient of Variation 31.94 |
Primary
Area Under the Serum Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of Dinutuximab Beta
Time frame: From Cycle 1 Day 1 pre-dose to Cycle 2 Day 1 pre-dose (Each cycle is 35 Days)
Population: Pharmacokinetic (PK) Analysis Set was defined as participants who had at least 1 available postbaseline PK data in the Safety Analysis Set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dinutuximab Beta + 13-cis-Retinoic Acid | Area Under the Serum Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of Dinutuximab Beta | 3956.3 hours*micrograms/milliliter (h*ug/mL) | Geometric Coefficient of Variation 33.11 |
Primary
Clearance (CL) of Dinutuximab Beta
Time frame: From Cycle 1 Day 1 pre-dose to Cycle 2 Day 1 pre-dose (Each cycle is 35 Days)
Population: Pharmacokinetic (PK) Analysis Set was defined as participants who had at least 1 available postbaseline PK data in the Safety Analysis Set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dinutuximab Beta + 13-cis-Retinoic Acid | Clearance (CL) of Dinutuximab Beta | 17.19 mL/h | Geometric Coefficient of Variation 34.627 |
Primary
Half-Life (t1/2) of Dinutuximab Beta
Time frame: From Cycle 1 Day 1 pre-dose to Cycle 2 Day 1 pre-dose (Each cycle is 35 Days)
Population: Pharmacokinetic (PK) Analysis Set was defined as participants who had at least 1 available postbaseline PK data in the Safety Analysis Set.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Dinutuximab Beta + 13-cis-Retinoic Acid | Half-Life (t1/2) of Dinutuximab Beta | 253.9 hours |
Primary
Maximum Observed Serum Concentration (Cmax) of Dinutuximab Beta
Time frame: From Cycle 1 Day 1 pre-dose to Cycle 2 Day 1 pre-dose (Each cycle is 35 Days)
Population: Pharmacokinetic (PK) Analysis Set was defined as participants who had at least 1 available postbaseline PK data in the Safety Analysis Set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dinutuximab Beta + 13-cis-Retinoic Acid | Maximum Observed Serum Concentration (Cmax) of Dinutuximab Beta | 13.49 ug/mL | Geometric Coefficient of Variation 32.682 |
Primary
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.
Time frame: From the first dose of study drug(s) to 40 days after the last dose; up to approximately 1 year and 1 month
Population: The Safety Analysis Set included all participants who received at least one dose of dinutuximab beta.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dinutuximab Beta + 13-cis-Retinoic Acid | Number of Participants With Adverse Events (AEs) | Participants With At Least 1 TEAE | 8 Participants |
| Dinutuximab Beta + 13-cis-Retinoic Acid | Number of Participants With Adverse Events (AEs) | Participants with Serious TEAEs | 1 Participants |
Primary
Time to Maximum Serum Concentration (Tmax) of Dinutuximab Beta
Time frame: From Cycle 1 Day 1 pre-dose to Cycle 2 Day 1 pre-dose (Each cycle is 35 Days)
Population: Pharmacokinetic (PK) Analysis Set was defined as participants who had at least 1 available postbaseline PK data in the Safety Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dinutuximab Beta + 13-cis-Retinoic Acid | Time to Maximum Serum Concentration (Tmax) of Dinutuximab Beta | 240.4 hours |
Primary
Volume of Distribution at Steady State (Vss) of Dinutuximab Beta
Time frame: From Cycle 1 Day 1 pre-dose to Cycle 2 Day 1 pre-dose (Each cycle is 35 Days)
Population: Pharmacokinetic (PK) Analysis Set was defined as participants who had at least 1 available postbaseline PK data in the Safety Analysis Set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dinutuximab Beta + 13-cis-Retinoic Acid | Volume of Distribution at Steady State (Vss) of Dinutuximab Beta | 3594.0 mL | Geometric Coefficient of Variation 37.12 |
Primary
Volume of Distribution During Terminal Phase (Vz) of Dinutuximab Beta
Time frame: From Cycle 1 Day 1 pre-dose to Cycle 2 Day 1 pre-dose (Each cycle is 35 Days)
Population: Pharmacokinetic (PK) Analysis Set was defined as participants who had at least 1 available postbaseline PK data in the Safety Analysis Set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dinutuximab Beta + 13-cis-Retinoic Acid | Volume of Distribution During Terminal Phase (Vz) of Dinutuximab Beta | 6295.9 mL | Geometric Coefficient of Variation 48.87 |