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

NCT06395103 | Recruiting Phase 1 DMC FDA Drug

• 6 other identifiers: 9999-01AMK-9999-01ALIGHTBEAM-U012023-507178-41-00U1111-1295-3459jRCT2031250824
• Study Type: interventional
• Target: 90
• Locations: 23 countries
• Sites: 67

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  Up to approximately 54 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.

  Up to approximately 54 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.

  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.

  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.

  Up to approximately 54 months

Secondary Outcomes (20)

• Part 1 and Part 2: Area Under the Curve (AUC) of Total Antibody

  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

  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: Plasma Trough Concentration (Ctrough) of Total Antibody

  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: Apparent Terminal Half-life (t1/2) of Total Antibody

  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: AUC of Antibody-Drug Conjugate (ADC)

  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)

Study Arms (1)

Zilovertamab vedotin

EXPERIMENTAL

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

Zilovertamab vedotin BIOLOGICAL

Administered via IV infusion

Also known as: MK-2140, VLS-101

Zilovertamab vedotin

Eligibility Criteria

• Age: 6 Months - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (67)

Children's Hospital Los Angeles ( Site 1006)

Los Angeles, California, 90027, United States

RECRUITING

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

Aurora, Colorado, 80045, United States

RECRUITING

Yale New Haven Hospital ( Site 1012)

New Haven, Connecticut, 06510, United States

RECRUITING

Johns Hopkins All Children's Hospital ( Site 1025)

St. Petersburg, Florida, 33701, United States

RECRUITING

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

Iowa City, Iowa, 52242, United States

RECRUITING

Dana-Farber Cancer Institute ( Site 1013)

Boston, Massachusetts, 02215, United States

RECRUITING

Corewell Health ( Site 1001)

Grand Rapids, Michigan, 49503, United States

RECRUITING

Children's Mercy Hospital ( Site 1024)

Kansas City, Missouri, 64108, United States

RECRUITING

Rutgers Cancer Institute of New Jersey ( Site 1008)

New Brunswick, New Jersey, 08903, United States

RECRUITING

Memorial Sloan Kettering Cancer Center ( Site 1010)

New York, New York, 10065, United States

RECRUITING

New York Medical College ( Site 1023)

Valhalla, New York, 10595, United States

RECRUITING

Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 1003)

Fargo, North Dakota, 58102, United States

RECRUITING

Oregon Health and Science University ( Site 1004)

Portland, Oregon, 97239, United States

RECRUITING

Children's Hospital of Philadelphia (CHOP) ( Site 1021)

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Sanford Children's Hospital-Sanford Children's Specialty Clinic ( Site 1015)

Sioux Falls, South Dakota, 57105, United States

RECRUITING

University of Texas MD Anderson Cancer Center ( Site 1007)

Houston, Texas, 77030, United States

RECRUITING

Intermountain - Primary Children's Hospital ( Site 1014)

Salt Lake City, Utah, 84113, United States

RECRUITING

Sydney Children's Hospital ( Site 1997)

Randwick, New South Wales, 2031, Australia

RECRUITING

Queensland Children's Hospital-Oncology & Haematology ( Site 1996)

Brisbane, Queensland, 4101, Australia

RECRUITING

UZ Gent ( Site 1428)

Ghent, Oost-Vlaanderen, 9000, Belgium

RECRUITING

Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 1268)

Curitiba, Paraná, 81520-060, Brazil

COMPLETED

Hospital de Clinicas de Porto Alegre ( Site 1265)

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

RECRUITING

Fundação Pio XII - Hospital de Câncer de Barretos ( Site 1264)

Barretos, São Paulo, 14784400, Brazil

RECRUITING

Fundação Faculdade Regional de Medicina de São José do Rio Preto-Centro Integrado de Pesquisa ( Site 1267)

São José do Rio Preto, São Paulo, 15090000, Brazil

RECRUITING

McGill University Health Centre-Pediatric HematologyOncology ( Site 1223)

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Hospital Luis Calvo Mackenna ( Site 1879)

Santiago, Region M. de Santiago, 7500539, Chile

RECRUITING

Hospital Carlos Van Buren ( Site 1880)

Valparaíso, Región de Valparaíso, 2341131, Chile

RECRUITING

Hospital Clínico Regional Dr. Guillermo Grant Benavente ( Site 1881)

Concepción, Región del Biobío, 4070038, Chile

RECRUITING

Hospital Pablo Tobon Uribe ( Site 1923)

Medellín, Antioquia, 050034, Colombia

RECRUITING

Clinica de la Costa S.A.S.-Clinical Research Oncology & Hematology -Pediatric ( Site 1924)

Barranquilla, Atlántico, 080020, Colombia

RECRUITING

IMAT S.A.S ( Site 1921)

Montería, Departamento de Córdoba, 230002, Colombia

RECRUITING

Detska nemocnice FN Brno ( Site 1388)

Brno, Brno-mesto, 613 00, Czechia

RECRUITING

Fakultni nemocnice v Motole-Klinika detske hematologie a onkologie ( Site 1387)

Prague, Praha 5, 150 00, Czechia

RECRUITING

Rigshospitalet-Department of paediatrics and adolescent medicine, Section of Paed haem-onc ( Site 1467)

Copenhagen, Capital Region, DK-2100, Denmark

RECRUITING

CHU de Bordeaux. Hopital Pellegrin ( Site 1105)

Bordeaux, Aquitaine, 33076, France

RECRUITING

CENTRE LEON BERARD-IHOPE (pediatrric oncology) ( Site 1100)

Lyon, Auvergne-Rhône-Alpes, 69373, France

RECRUITING

Centre Hospitalier Universitaire de Nantes - Hôpital Femme-Enfant-Adolescent Chu De Nantes ( Site 1104)

Nantes, Loire-Atlantique, 44093, France

RECRUITING

Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone ( Site 1102)

Marseille, Provence-Alpes-Côte d'Azur Region, 13005, France

RECRUITING

Gustave Roussy ( Site 1103)

Villejuif, Île-de-France Region, 94805, France

RECRUITING

Universitaetsklinikum Tuebingen ( Site 1142)

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

Universitaetsklinikum Koeln. Klinik und Poliklinik ( Site 1145)

Cologne, North Rhine-Westphalia, 50937, Germany

RECRUITING

Universitätsklinikum Münster - Albert Schweitzer Campus-Pädiatrische Hämatologie und Onkologie ( Site 1141)

Münster, North Rhine-Westphalia, 48149, Germany

RECRUITING

Charité Campus Virchow-Klinikum-Klinik für Pädiatrie mit Schwerpunkt Hämatologie und Onkologie ( Site 1143)

Berlin, 13353, Germany

RECRUITING

Aghia Sophia Children's Hospital-First Department of Pediatrics, National and Kapodistrian Universi ( Site 1797)

Athens, Attica, 115 27, Greece

RECRUITING

Semmelweis Egyetem ( Site 1838)

Budapest, 1085, Hungary

RECRUITING

Rambam Health Care Campus-Pediatric Hemato-Oncology ( Site 1674)

Haifa, 3109601, Israel

RECRUITING

Sheba Medical Center ( Site 1675)

Ramat Gan, 5265601, Israel

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori-Pediatric Oncology ( Site 1552)

Milan, Lombardy, 20133, Italy

RECRUITING

Ospedale Pediatrico Bambino Gesù IRCCS-Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica ( Site 1553)

Rome, Roma, 00165, Italy

RECRUITING

Ospedale Infantile Regina Margherita-S.C. Oncoematologia Pediatrica ( Site 1551)

Torino, 10126, Italy

RECRUITING

Prinses Maxima Centrum voor Kinderoncologie ( Site 1510)

Utrecht, 3584 CS, Netherlands

RECRUITING

Narodny ustav detskych chorob ( Site 1592)

Bratislava, Bratislava Region, 831 01, Slovakia

RECRUITING

Seoul National University Hospital-Pediatrics ( Site 1972)

Seoul, 03080, South Korea

RECRUITING

Asan Medical Center-Pediatrics - Pedicatric Oncology ( Site 1973)

Seoul, 05505, South Korea

RECRUITING

Hospital Sant Joan de Déu-Pediatric Oncology Department ( Site 1717)

Esplugas de Llobregat, Barcelona, 08950, Spain

RECRUITING

Hospital Infantil Universitario Niño Jesús-Servicio de Onco-Hematología Pediátrica ( Site 1715)

Madrid, Madrid, Comunidad de, 28009, Spain

RECRUITING

Hospital Universitari Vall d'Hebron-Servei de Hematologia i Oncologia Pediatrica ( Site 1716)

Barcelona, 08035, Spain

RECRUITING

Sahlgrenska Universitetssjukhuset ( Site 1634)

Gothenburg, Västra Götaland County, 416 85, Sweden

RECRUITING

National Taiwan University Hospital ( Site 1983)

Taipei, 10002, Taiwan

RECRUITING

Ege Universitesi Hastanesi ( Site 1963)

Bornova, İzmir, 35100, Turkey (Türkiye)

RECRUITING

Hacettepe Universite Hastaneleri ( Site 1961)

Ankara, 06230, Turkey (Türkiye)

RECRUITING

Ankara Bilkent Şehir Hastanesi ( Site 1962)

Ankara, 06800, Turkey (Türkiye)

RECRUITING

Birmingham Children's Hospital-Oncology/Haematology ( Site 1349)

Birmingham, England, B4 6NH, United Kingdom

RECRUITING

Royal Victoria Infirmary-Great North Children's Hospital ( Site 1348)

Newcastle upon Tyne, England, NE1 4PL, United Kingdom

RECRUITING

University College London Hospital ( Site 1350)

London, London, City of, NW1 2PG, United Kingdom

RECRUITING

Royal Marsden Hospital (Sutton)-Drug Development Unit ( Site 1347)

Sutton, Surrey, SM2 5PT, United Kingdom

RECRUITING

University Hospital of Wales ( Site 1346)

Cardiff, CF14 4XW, United Kingdom

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Neuroblastoma; Sarcoma, Ewing

Condition Hierarchy (Ancestors)

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

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2024
• First Posted: May 1, 2024
• Study Start: August 16, 2024
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): March 31, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (4); BR (4); CA (1); DK (1); CO (3); CZ (2); KR (2); SE (1); HU (1); IL (2); BE (1); SL (1); TU (3); NL (1); IT (3); CL (3); AU (2); GB (5); US (17); ES (3); TW (1); FR (5); GR (1)