Clinical trial NCT06395103: Substudy 01A: Zilovertamab Vedotin in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors (MK-9999-01A/LIGHTBEAM-U01)
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: B-cell Acute Lymphoblastic Leukemia
Diffuse Large B-cell Lymphoma
Burkitt Lymphoma
Neuroblastoma
Ewing Sarcoma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2024-05-01
Enrollment: 90
Sex: ALL
Minimum age (years): 6
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Number of Participants from 1 to <18 years of Age Who Experience a Dose-Limiting Toxicity (DLT)
timeFrame: Up to 42 days
measure: Part 1: Number of Participants from 1 to <18 years of Age Who Experience One or More Adverse Events (AEs)
timeFrame: Up to approximately 60 months
measure: Part 1: Number of Participants from 1 to <18 years of Age Who Discontinue Study Treatment Due to AEs
timeFrame: Up to approximately 60 months
measure: Part 1: Number of Participants from 1 to <18 years of Age Who Receive Dose Modification Due to AEs
timeFrame: Up to approximately 60 months
measure: Part 1 and Part 2: Objective Response (OR) for Participants with B-Cell Acute Lymphoblastic Leukemia (B-ALL)
timeFrame: Up to approximately 60 months
measure: Part 1 and Part 2: OR for Participants with Diffuse Large B-Cell Lymphoma (DLBCL)/Burkitt Lymphoma, Neuroblastoma, and Ewing Sarcoma
timeFrame: Up to approximately 60 months
Secondary outcomes:
measure: Part 1 and Part 2: Area Under the Curve (AUC) of Total Antibody
timeFrame: 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)
measure: Part 1 and Part 2: Maximum Plasma Concentration (Cmax) of Total Antibody
timeFrame: 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)
measure: Part 1 and Part 2: Plasma Trough Concentration (Ctrough) of Total Antibody
timeFrame: 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)
measure: Part 1 and Part 2: Apparent Terminal Half-life (t1/2) of Total Antibody
timeFrame: 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)
measure: Part 1 and Part 2: AUC of Antibody-Drug Conjugate (ADC)
timeFrame: 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)
measure: Part 1 and Part 2: Cmax of Antibody-Drug Conjugate (ADC)
timeFrame: 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)
measure: Part 1 and Part 2: Ctrough of Antibody-Drug Conjugate (ADC)
timeFrame: 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)
measure: Part 1 and Part 2: t1/2 of Antibody-Drug Conjugate (ADC)
timeFrame: 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)
measure: Part 1 and Part 2: AUC of Monomethyl Auristatin E (MMAE)
timeFrame: 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)
measure: Part 1 and Part 2: Cmax of Monomethyl Auristatin E (MMAE)
timeFrame: 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)
measure: Part 1 and Part 2: Ctrough of Monomethyl Auristatin E (MMAE)
timeFrame: 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)
measure: Part 1 and Part 2: t1/2 of Monomethyl Auristatin E (MMAE)
timeFrame: 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)
measure: Part 2: Number of Participants Who Experience One or More Adverse Events (AEs)
timeFrame: Up to approximately 60 months
measure: Part 2: Number of Participants Who Discontinue Study Treatment Due to AEs
timeFrame: Up to approximately 60 months
measure: Part 2: Number of Participants Who Receive Dose Modification Due to AEs
timeFrame: Up to approximately 60 months
measure: Part 1 and Part 2: Incidence of Antidrug Antibodies (ADAs) to Zilovertamab Vedotin
timeFrame: 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)
measure: Part 1 and Part 2: Duration of Response (DOR)
timeFrame: Up to approximately 60 months
measure: Part 1 and Part 2: Percentage of Participants with DLBCL/Burkitt Lymphoma Who Receive Stem Cell Transplant (SCT)
timeFrame: Up to approximately 60 months
measure: Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive SCT
timeFrame: Up to approximately 60 months
measure: Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive Chimeric Antigen Receptor T (CAR-T)
timeFrame: Up to approximately 60 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles ( Site 1006)
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado-Center for Cancer and Blood Disorders ( Site 1016)
state: Colorado
city: New Haven
country: United States
facility: Yale-New Haven Hospital ( Site 1012)
state: Connecticut
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital ( Site 1025)
state: Florida
city: Iowa City
country: United States
facility: University of Iowa-Holden Comprehensive Cancer Center ( Site 1017)
state: Iowa
city: Boston
country: United States
facility: Dana-Farber Cancer Institute ( Site 1013)
state: Massachusetts
city: Grand Rapids
country: United States
facility: Corewell Health ( Site 1001)
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospital ( Site 1024)
state: Missouri
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey ( Site 1008)
state: New Jersey
city: Valhalla
country: United States
facility: New York Medical College ( Site 1023)
state: New York
city: Fargo
country: United States
facility: Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 1003)
state: North Dakota
city: Portland
country: United States
facility: Oregon Health and Science University ( Site 1004)
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia (CHOP) ( Site 1021)
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Children's Hospital-Sanford Children's Specialty Clinic ( Site 1015)
state: South Dakota
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center ( Site 1007)
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain - Primary Children's Hospital ( Site 1014)
state: Utah
city: Randwick
country: Australia
facility: Sydney Children's Hospital-Kids Cancer Centre ( Site 1997)
state: New South Wales
city: Brisbane
country: Australia
facility: Queensland Children's Hospital-Oncology & Haematology ( Site 1996)
state: Queensland
city: Gent
country: Belgium
facility: UZ Gent ( Site 1428)
state: Oost-Vlaanderen
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 1268)
state: Parana
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre ( Site 1265)
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Fundação Pio XII - Hospital de Câncer de Barretos ( Site 1264)
state: Sao Paulo
city: São José do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto-Centro Integrado de Pesquisa ( Site 1267)
state: Sao Paulo
city: Valparaíso
country: Chile
facility: Hospital Carlos Van Buren ( Site 1880)
state: Valparaiso
city: Medellin
country: Colombia
facility: Hospital Pablo Tobon Uribe ( Site 1923)
state: Antioquia
city: Barranquilla
country: Colombia
facility: Clinica de la Costa S.A.S.-Clinical Research Oncology & Hematology -Pediatric ( Site 1924)
state: Atlantico
city: Monteria
country: Colombia
facility: IMAT S.A.S ( Site 1921)
state: Cordoba
city: Copenhagen
country: Denmark
facility: Rigshospitalet-Department of paediatrics and adolescent medicine, Section of Paed haem-onc ( Site 1467)
state: Hovedstaden
city: Bordeaux
country: France
facility: CHU de Bordeaux. Hopital Pellegrin ( Site 1105)
state: Aquitaine
city: Villejuif
country: France
facility: Gustave Roussy ( Site 1103)
state: Ile-de-France
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes - Hôpital Femme-Enfant-Adolescent Chu De Nantes ( Site 1104)
state: Pays-de-la-Loire
city: Lyon
country: France
facility: CENTRE LEON BERARD-IHOPE (pediatrric oncology) ( Site 1100)
state: Rhone-Alpes
city: Münster
country: Germany
facility: Universitätsklinikum Münster - Albert Schweitzer Campus-Pädiatrische Hämatologie und Onkologie ( Site 1141)
state: Nordrhein-Westfalen
city: Athens
country: Greece
facility: Aghia Sophia Children's Hospital-First Department of Pediatrics, National and Kapodistrian Universi ( Site 1797)
state: Attiki
city: Budapest
country: Hungary
facility: Semmelweis Egyetem ( Site 1838)
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Pediatric Hemato-Oncology ( Site 1674)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center ( Site 1675)
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori-Pediatric Oncology ( Site 1552)
state: Lombardia
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesù IRCCS-Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica ( Site 1553)
state: Roma
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital-Pediatrics ( Site 1972)
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center-Pediatrics - Pedicatric Oncology ( Site 1973)
city: Utrecht
country: Netherlands
facility: Prinses Maxima Centrum voor Kinderoncologie ( Site 1510)
city: Esplugas De Llobregat
country: Spain
facility: Hospital Sant Joan de Déu-Pediatric Oncology Department ( Site 1717)
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesús-Servicio de Onco-Hematología Pediátrica ( Site 1715)
state: Madrid, Comunidad De
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron-Servei de Hematologia i Oncologia Pediatrica ( Site 1716)
city: Gothenburg
country: Sweden
facility: Prövningsenhet barn, Sahlgrenska Universitetssjukhuset ( Site 1634)
state: Vastra Gotalands Lan
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 1983)
city: Ankara
country: Turkey
facility: Hacettepe Universite Hastaneleri ( Site 1961)
city: Ankara
country: Turkey
facility: Ankara Bilkent Şehir Hastanesi ( Site 1962)
city: İzmir
country: Turkey
facility: Ege Universitesi Hastanesi ( Site 1963)
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary-Great North Children's Hospital ( Site 1348)
state: England
city: London
country: United Kingdom
facility: University College London Hospital ( Site 1350)
state: London, City Of
city: Sutton.
country: United Kingdom
facility: Royal Marsden Hospital (Sutton)-Drug Development Unit ( Site 1347)
state: Surrey
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales ( Site 1346)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: