Substudy 01A is part of a platform study. The purpose of this study is to assess the efficacy and safety of zilovertamab vedotin in pediatric participants with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphoma (DLBCL)/Burkitt lymphoma, or neuroblastoma and in pediatric and young adult participants with Ewing sarcoma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
90
Administered via IV infusion
Children's Hospital Los Angeles ( Site 1006)
Los Angeles, California, United States
RECRUITINGChildren's Hospital Colorado-Center for Cancer and Blood Disorders ( Site 1016)
Aurora, Colorado, United States
RECRUITINGYale New Haven Hospital ( Site 1012)
New Haven, Connecticut, United States
RECRUITINGJohns Hopkins All Children's Hospital ( Site 1025)
St. Petersburg, Florida, United States
RECRUITINGUniversity of Iowa-Holden Comprehensive Cancer Center ( Site 1017)
Iowa City, Iowa, United States
RECRUITINGDana-Farber Cancer Institute ( Site 1013)
Boston, Massachusetts, United States
RECRUITINGCorewell Health ( Site 1001)
Grand Rapids, Michigan, United States
RECRUITINGChildren's Mercy Hospital ( Site 1024)
Kansas City, Missouri, United States
RECRUITINGRutgers Cancer Institute of New Jersey ( Site 1008)
New Brunswick, New Jersey, United States
RECRUITINGNew York Medical College ( Site 1023)
Valhalla, New York, United States
RECRUITING...and 56 more locations
Part 1: Number of Participants from 1 to <18 years of Age Who Experience a Dose-Limiting Toxicity (DLT)
Number of participants experiencing toxicities that are possibly, probably, or definitely related to study therapy; that meet pre-defined severity criteria; and result in a change in the given dose.
Time frame: Up to 42 days
Part 1: Number of Participants from 1 to <18 years of Age Who Experience One or More Adverse Events (AEs)
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants in Part 1 who experience at least 1 AE will be presented.
Time frame: Up to approximately 60 months
Part 1: Number of Participants from 1 to <18 years of Age Who Discontinue Study Treatment Due to AEs
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants in Part 1 who discontinue study treatment due to an AE will be presented.
Time frame: Up to approximately 60 months
Part 1: Number of Participants from 1 to <18 years of Age Who Receive Dose Modification Due to AEs
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants in Part 1 who receive a dose modification due to an AE will be presented.
Time frame: Up to approximately 60 months
Part 1 and Part 2: Objective Response (OR) for Participants with B-Cell Acute Lymphoblastic Leukemia (B-ALL)
OR for participants with B-ALL is defined as complete response (CR) or complete response with incomplete hematologic recovery (CRi) based on investigator's assessment per Ponte-di-Legno Consortium criteria. For Part 1 and Part 2, the OR for participants with B-ALL as assessed by investigator will be presented.
Time frame: Up to approximately 60 months
Part 1 and Part 2: OR for Participants with Diffuse Large B-Cell Lymphoma (DLBCL)/Burkitt Lymphoma, Neuroblastoma, and Ewing Sarcoma
OR for participants with DLBCL/Burkitt lymphoma, neuroblastoma, and Ewing sarcoma is defined as complete response (CR) or partial response (PR) based on investigator's assessment per International Pediatric Non-Hodgkin Lymphoma (IPNHL) Response Criteria for participants with DLBCL/Burkitt lymphoma, per International Neuroblastoma Response Criteria (INRC) for neuroblastoma, and per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for Ewing sarcoma. For Part 1 and Part 2, the OR for participants with DLBCL/Burkitt lymphoma, neuroblastoma, and Ewing sarcoma as assessed by investigator will be presented.
Time frame: Up to approximately 60 months
Part 1 and Part 2: Area Under the Curve (AUC) of Total Antibody
Blood samples collected at designated time points will be used to determine the AUC of total antibody.
Time frame: Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Part 1 and Part 2: Maximum Plasma Concentration (Cmax) of Total Antibody
Blood samples collected at designated time points will be used to determine the Cmax of total antibody.
Time frame: Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Part 1 and Part 2: Plasma Trough Concentration (Ctrough) of Total Antibody
Blood samples collected at designated time points will be used to determine the Ctrough of total antibody.
Time frame: Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Part 1 and Part 2: Apparent Terminal Half-life (t1/2) of Total Antibody
Blood samples collected at designated time points will be used to determine the t1/2 of total antibody.
Time frame: Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Part 1 and Part 2: AUC of Antibody-Drug Conjugate (ADC)
Blood samples collected at designated time points will be used to determine the AUC of ADC.
Time frame: Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Part 1 and Part 2: Cmax of Antibody-Drug Conjugate (ADC)
Blood samples collected at designated time points will be used to determine the Cmax of ADC.
Time frame: ose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Part 1 and Part 2: Ctrough of Antibody-Drug Conjugate (ADC)
Blood samples collected at designated time points will be used to determine the Ctrough of ADC.
Time frame: Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Part 1 and Part 2: t1/2 of Antibody-Drug Conjugate (ADC)
Blood samples collected at designated time points will be used to determine the t1/2 of ADC.
Time frame: Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Part 1 and Part 2: AUC of Monomethyl Auristatin E (MMAE)
Blood samples collected at designated time points will be used to determine the AUC of MMAE.
Time frame: Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Part 1 and Part 2: Cmax of Monomethyl Auristatin E (MMAE)
Blood samples collected at designated time points will be used to determine the Cmax of MMAE.
Time frame: Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Part 1 and Part 2: Ctrough of Monomethyl Auristatin E (MMAE)
Blood samples collected at designated time points will be used to determine the Ctrough of MMAE.
Time frame: Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Part 1 and Part 2: t1/2 of Monomethyl Auristatin E (MMAE)
Blood samples collected at designated time points will be used to determine the t1/2 of MMAE.
Time frame: Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Part 2: Number of Participants Who Experience One or More Adverse Events (AEs)
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants in Part 2 who experience at least 1 AE will be presented.
Time frame: Up to approximately 60 months
Part 2: Number of Participants Who Discontinue Study Treatment Due to AEs
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants in Part 2 who discontinue study treatment due to an AE will be presented.
Time frame: Up to approximately 60 months
Part 2: Number of Participants Who Receive Dose Modification Due to AEs
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants in Part 2 who receive a dose modification due to an AE will be presented.
Time frame: Up to approximately 60 months
Part 1 and Part 2: Incidence of Antidrug Antibodies (ADAs) to Zilovertamab Vedotin
Blood samples collected at designated timepoints will be used to determine the ADA response to zilovertamab vedotin. The incidence of ADAs over time will be presented.
Time frame: Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter. Each cycle is 21 days. (Up to approximately 60 months)
Part 1 and Part 2: Duration of Response (DOR)
DOR is defined as the time from the first documented evidence of CR/CRi for B-ALL or CR/PR for DLBCL/Burkitt lymphoma, Ewing sarcoma, and neuroblastoma until disease progression or death due to any cause, whichever occurs first. For participants under 1-year of age, the time from the first dose will start from the first dose a participant receives during Part 2.
Time frame: Up to approximately 60 months
Part 1 and Part 2: Percentage of Participants with DLBCL/Burkitt Lymphoma Who Receive Stem Cell Transplant (SCT)
The percentage of participants with DLBCL/Burkitt Lymphoma who go on to receive SCT will be presented.
Time frame: Up to approximately 60 months
Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive SCT
The percentage of participants with B-ALL who go on to receive SCT will be presented.
Time frame: Up to approximately 60 months
Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive Chimeric Antigen Receptor T (CAR-T)
The percentage of participants with B-ALL who go on to receive CAR-T will be presented.
Time frame: Up to approximately 60 months
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