Substudy 01A: Zilovertamab Vedotin in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors (MK-9999-01A/LIGHTBEAM-U01)

Browse trials for

• Burkitt Lymphoma 391
• Lymphoma, Large B-Cell, Diffuse 1,390
• Neuroblastoma 625
• Sarcoma, Ewing 287

Study arms

• Experimental
  Zilovertamab vedotin

  Participants receive escalating doses of zilovertamab vedotin via intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks).

  Biological: Zilovertamab vedotin

Interventions

• BiologicalZilovertamab vedotin

  Administered via IV infusion

  Also known as: MK-2140, VLS-101

Primary outcomes

1. 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

2. 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 54 months

3. 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 54 months

4. 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 54 months

5. 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 54 months

6. 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 54 months

Secondary outcomes

1. 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 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months)

2. 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 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months)

3. 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 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months)

4. 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 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months)

5. 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 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months)

6. Part 1 and Part 2: Cmax of ADC

   Blood samples collected at designated time points will be used to determine the Cmax of ADC.

   Time frame: Predose on Day 1 of Cycles 1 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months)

7. Part 1 and Part 2: Ctrough of 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 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months)

8. Part 1 and Part 2: t1/2 of 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 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months)

9. 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 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months)

10. Part 1 and Part 2: Cmax of 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 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months)

11. Part 1 and Part 2: Ctrough of 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 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months)

12. Part 1 and Part 2: t1/2 of 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 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months)

13. Part 2: Number of Participants Who Experience One or More 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 54 months

14. 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 54 months

15. 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 54 months

16. 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 54 months)

17. 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 54 months

18. 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 54 months

19. 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 54 months

20. 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 54 months

Related links

• Merck Clinical Trials Information ↗
• Plain Language Summary ↗

Individual participant data

Plan to share: Yes — https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf