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

Phase 2RecruitingNCT06395103

Merck Sharp & Dohme LLC90 enrolled

Overview

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

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

B-cell Acute Lymphoblastic Leukemia Diffuse Large B-cell Lymphoma Burkitt Lymphoma Neuroblastoma Ewing Sarcoma

Interventions

Zilovertamab vedotinBIOLOGICAL

Administered via IV infusion

Eligibility

Sex: ALLMin age: 6 MonthsMax age: 25 Years

Medical Language ↔ Plain English

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.

Locations (71)

Children's Hospital Los Angeles ( Site 1006)

Los Angeles, California, United States

RECRUITING

Children's Hospital Colorado-Center for Cancer and Blood Disorders ( Site 1016)

Aurora, Colorado, United States

RECRUITING

Yale New Haven Hospital ( Site 1012)

New Haven, Connecticut, United States

RECRUITING

Johns Hopkins All Children's Hospital ( Site 1025)

St. Petersburg, Florida, United States

Outcomes

Primary Outcomes

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 54 months

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

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

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

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

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)

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.

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.

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.

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.

Central Contacts

Toll Free Number

CONTACT

1-888-577-8839 Trialsites@msd.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

University of Iowa-Holden Comprehensive Cancer Center ( Site 1017)

Iowa City, Iowa, United States

RECRUITING

Dana-Farber Cancer Institute ( Site 1013)

Boston, Massachusetts, United States

RECRUITING

Corewell Health ( Site 1001)

Grand Rapids, Michigan, United States

RECRUITING

Children's Mercy Hospital ( Site 1024)

Kansas City, Missouri, United States

RECRUITING

Rutgers Cancer Institute of New Jersey ( Site 1008)

New Brunswick, New Jersey, United States

RECRUITING

Memorial Sloan Kettering Cancer Center ( Site 1010)

New York, New York, United States

RECRUITING

...and 61 more locations

Part 1 and Part 2: Cmax of ADC

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

Part 1 and Part 2: Ctrough of ADC

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

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.

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.

Part 1 and Part 2: Cmax of MMAE

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

Part 1 and Part 2: Ctrough of MMAE

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

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.

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

Time frame: Up to approximately 54 months

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

Time frame: Up to approximately 54 months

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

Time frame: Up to approximately 54 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 54 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 54 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 54 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 54 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 54 months