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NCT Number: NCT06395103

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

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.

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Key information

Conditions

B-cell Acute Lymphoblastic Leukemia Burkitt Lymphoma DNA Virus Infections Diffuse Large B-cell Lymphoma Epstein-Barr Virus Infections Ewing Sarcoma Hemic and Lymphatic Diseases Herpesviridae Infections Immune System Diseases Immunoproliferative Disorders Infections Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms, Bone Tissue Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neuroblastoma Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Neuroectodermal Tumors, Primitive, Peripheral Osteosarcoma Sarcoma Sarcoma, Ewing Tumor Virus Infections Virus Diseases

Age range

6 month–25 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Sydney Children's Hospital ( Site 1997), Randwick, New South Wales, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion criteria

  • For hematological malignancies: Confirmed diagnosis of B-precursor B-ALL or DLBCL/Burkitt lymphoma according to World Health Organization (WHO) classification of neoplasms of the lymphoid tissues.
  • For solid tumor malignancies: Histologically confirmed diagnosis of neuroblastoma or Ewing sarcoma.

Exclusion criteria

  • History of solid organ transplant.
  • Clinically significant (ie, active) cardiovascular disease.
  • Known history of liver cirrhosis.
  • Ongoing Grade >1 peripheral neuropathy.
  • Demyelinating form of Charcot-Marie-Tooth disease.
  • Diagnosed with Down syndrome.
  • Ongoing graft-versus-host disease (GVHD) of any grade or receiving systemic GVHD treatment or prophylaxis.
  • History of human immunodeficiency virus (HIV) infection.
  • Contraindication or hypersensitivity to any of the study intervention components.
  • Received prior radiotherapy within 4 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities.
  • Ongoing, chronic corticosteroid therapy (exceeding 10 mg daily of prednisone equivalent). Prednisone equivalent dosing must have been stable for at least 4 weeks before Cycle 1 Day 1 (C1D1).
  • Received a strong cytochrome P450 3A4 (CYP3A4) inhibitor within 7 days or a strong CYP3A4 inducer within 14 days before the start of study intervention or expected requirement for chronic use of a strong CYP3A4 inhibitor or inducer during the study intervention period and for 30 days after the last dose of study intervention
  • Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention (except for prophylactic intrathecal chemotherapy and/or cytoreductive therapy with steroids/hydroxyurea.
  • Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
  • Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
  • Known additional malignancy that is progressing or has required active treatment within the past 1 year.
  • Active infection requiring systemic therapy.
  • Known history of Hepatitis B or known active Hepatitis C virus infection.
  • Participants who have not adequately recovered from major surgery or have ongoing surgical complications.

Treatment and study plan

Zilovertamab vedotin

Biological

Administered via IV infusion

Other names: 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)

    Time frame: Up to 42 days

    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.

  2. Part 1: Number of Participants from 1 to <18 years of Age Who Experience One or More Adverse Events (AEs)

    Time frame: Up to approximately 54 months

    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.

  3. Part 1: Number of Participants from 1 to <18 years of Age Who Discontinue Study Treatment Due to AEs

    Time frame: Up to approximately 54 months

    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.

  4. Part 1: Number of Participants from 1 to <18 years of Age Who Receive Dose Modification Due to AEs

    Time frame: Up to approximately 54 months

    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.

  5. Part 1 and Part 2: Objective Response (OR) for Participants with B-Cell Acute Lymphoblastic Leukemia (B-ALL)

    Time frame: Up to approximately 54 months

    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.

  6. Part 1 and Part 2: OR for Participants with Diffuse Large B-Cell Lymphoma (DLBCL)/Burkitt Lymphoma, Neuroblastoma, and Ewing Sarcoma

    Time frame: Up to approximately 54 months

    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.

Secondary outcomes

  1. Part 1 and Part 2: Area Under the Curve (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)

    Blood samples collected at designated time points will be used to determine the AUC of total antibody.

  2. Part 1 and Part 2: Maximum Plasma Concentration (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)

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

  3. Part 1 and Part 2: Plasma Trough Concentration (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)

    Blood samples collected at designated time points will be used to determine the Ctrough of total antibody.

  4. Part 1 and Part 2: Apparent Terminal Half-life (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)

    Blood samples collected at designated time points will be used to determine the t1/2 of total antibody.

  5. Part 1 and Part 2: AUC of Antibody-Drug Conjugate (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)

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

  6. Part 1 and Part 2: 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)

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

  7. Part 1 and Part 2: 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)

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

  8. Part 1 and Part 2: 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)

    Blood samples collected at designated time points will be used to determine the t1/2 of ADC.

  9. Part 1 and Part 2: AUC of Monomethyl Auristatin E (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)

    Blood samples collected at designated time points will be used to determine the AUC of MMAE.

  10. Part 1 and Part 2: 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)

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

  11. Part 1 and Part 2: 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)

    Blood samples collected at designated time points will be used to determine the Ctrough of MMAE.

  12. Part 1 and Part 2: 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)

    Blood samples collected at designated time points will be used to determine the t1/2 of MMAE.

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

    Time frame: Up to approximately 54 months

    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.

  14. Part 2: Number of Participants Who Discontinue Study Treatment Due to AEs

    Time frame: Up to approximately 54 months

    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.

  15. Part 2: Number of Participants Who Receive Dose Modification Due to AEs

    Time frame: Up to approximately 54 months

    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.

  16. Part 1 and Part 2: Incidence of Antidrug Antibodies (ADAs) to Zilovertamab Vedotin

    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)

    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.

  17. Part 1 and Part 2: Duration of Response (DOR)

    Time frame: Up to approximately 54 months

    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.

  18. Part 1 and Part 2: Percentage of Participants with DLBCL/Burkitt Lymphoma Who Receive Stem Cell Transplant (SCT)

    Time frame: Up to approximately 54 months

    The percentage of participants with DLBCL/Burkitt Lymphoma who go on to receive SCT will be presented.

  19. Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive SCT

    Time frame: Up to approximately 54 months

    The percentage of participants with B-ALL who go on to receive SCT will be presented.

  20. Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive Chimeric Antigen Receptor T (CAR-T)

    Time frame: Up to approximately 54 months

    The percentage of participants with B-ALL who go on to receive CAR-T will be presented.

Study contacts

Contact information is provided by the study sponsor or research team.

Toll Free Number

CONTACT

[email protected]

1-888-577-8839

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

LIGHTBEAM-U01 Substudy 01A: A Phase 1/2 Substudy to Evaluate the Safety and Efficacy of Zilovertamab Vedotin in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors

Important dates

Study start
2024
Primary completion
2029
Study completion
2029
First posted
May 1, 2024
Registry last updated
Jul 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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