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

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.

Interventions

• Biological Zilovertamab vedotin
  Administered via IV infusion

Primary outcome measures

• 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]
• 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]
• 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) [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 [Time frame: Up to approximately 54 months]

Secondary outcome measures (12)

• 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)]
• 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)]
• 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)]
• 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)]
• 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)]
• 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)]
• 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)]
• 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)]
• 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)]
• 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)]
• 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)]
• 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)]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 17 centers

• Children's Hospital Los Angeles ( Site 1006) — Los Angeles
• Children's Hospital Colorado-Center for Cancer and Blood Disorders ( Site 1016) — Aurora
• Yale New Haven Hospital ( Site 1012) — New Haven
• Johns Hopkins All Children's Hospital ( Site 1025) — St. Petersburg
• University of Iowa-Holden Comprehensive Cancer Center ( Site 1017) — Iowa City
• Dana-Farber Cancer Institute ( Site 1013) — Boston
• Corewell Health ( Site 1001) — Grand Rapids
• Children's Mercy Hospital ( Site 1024) — Kansas City
• … and 9 more centers

France · 5 centers

• CHU de Bordeaux. Hopital Pellegrin ( Site 1105) — Bordeaux
• CENTRE LEON BERARD-IHOPE (pediatrric oncology) ( Site 1100) — Lyon
• Centre Hospitalier Universitaire de Nantes - Hôpital Femme-Enfant-Adolescent Chu De Nantes — Nantes
• Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone ( Site 1102) — Marseille
• Gustave Roussy ( Site 1103) — Villejuif

United Kingdom · 5 centers

• Birmingham Children's Hospital-Oncology/Haematology ( Site 1349) — Birmingham
• Royal Victoria Infirmary-Great North Children's Hospital ( Site 1348) — Newcastle upon Tyne
• University College London Hospital ( Site 1350) — London
• Royal Marsden Hospital (Sutton)-Drug Development Unit ( Site 1347) — Sutton
• University Hospital of Wales ( Site 1346) — Cardiff

Brazil · 4 centers

• Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 1268) — Curitiba
• Hospital de Clinicas de Porto Alegre ( Site 1265) — Porto Alegre
• Fundação Pio XII - Hospital de Câncer de Barretos ( Site 1264) — Barretos
• Fundação Faculdade Regional de Medicina de São José do Rio Preto-Centro Integrado de Pesqu — São José do Rio Preto

Germany · 4 centers

• Universitaetsklinikum Tuebingen ( Site 1142) — Tübingen
• Universitaetsklinikum Koeln. Klinik und Poliklinik ( Site 1145) — Cologne
• Universitätsklinikum Münster - Albert Schweitzer Campus-Pädiatrische Hämatologie und Onkol — Münster
• Charité Campus Virchow-Klinikum-Klinik für Pädiatrie mit Schwerpunkt Hämatologie und Onkol — Berlin

Spain · 4 centers

• Hospital Sant Joan de Déu-Pediatric Oncology Department ( Site 1717) — Esplugas de Llobregat
• Hospital Infantil Universitario Niño Jesús-Servicio de Onco-Hematología Pediátrica ( Site — Madrid
• Hospital Universitario y Politecnico La Fe de Valencia ( Site 1718) — Valencia
• Hospital Universitari Vall d'Hebron-Servei de Hematologia i Oncologia Pediatrica ( Site 17 — Barcelona

Australia · 3 centers

• Sydney Children's Hospital ( Site 1997) — Randwick
• Queensland Children's Hospital-Oncology & Haematology ( Site 1996) — Brisbane
• Royal Children's Hospital-Children's Cancer Centre ( Site 1994) — Melbourne

Canada · 3 centers

• Alberta Children's Hospital ( Site 1227) — Calgary
• The Hospital for Sick Children ( Site 1225) — Toronto
• McGill University Health Centre-Pediatric HematologyOncology ( Site 1223) — Montreal

Chile · 3 centers

• Hospital Clínico Regional Dr. Guillermo Grant Benavente ( Site 1881) — Concepción
• Hospital Luis Calvo Mackenna ( Site 1879) — Santiago
• Hospital Carlos Van Buren ( Site 1880) — Valparaíso

Colombia · 3 centers

• Hospital Pablo Tobon Uribe ( Site 1923) — Medellín
• Clinica de la Costa S.A.S.-Clinical Research Oncology & Hematology -Pediatric ( Site 1924) — Barranquilla
• IMAT S.A.S ( Site 1921) — Montería

Italy · 3 centers

• Fondazione IRCCS Istituto Nazionale dei Tumori-Pediatric Oncology ( Site 1552) — Milan
• Ospedale Pediatrico Bambino Gesù IRCCS-Dipartimento di Onco-Ematologia e Terapia Cellulare — Rome
• Ospedale Infantile Regina Margherita-S.C. Oncoematologia Pediatrica ( Site 1551) — Torino

Turkey (Türkiye) · 3 centers

• Ege Universitesi Hastanesi ( Site 1963) — Bornova
• Hacettepe Universite Hastaneleri ( Site 1961) — Ankara
• Ankara Bilkent Şehir Hastanesi ( Site 1962) — Ankara

Czechia · 2 centers

• Detska nemocnice FN Brno ( Site 1388) — Brno
• Fakultni nemocnice v Motole-Klinika detske hematologie a onkologie ( Site 1387) — Prague

Israel · 2 centers

• Rambam Health Care Campus-Pediatric Hemato-Oncology ( Site 1674) — Haifa
• Sheba Medical Center ( Site 1675) — Ramat Gan

South Korea · 2 centers

• Seoul National University Hospital-Pediatrics ( Site 1972) — Seoul
• Asan Medical Center-Pediatrics - Pedicatric Oncology ( Site 1973) — Seoul

Belgium · 1 center

• UZ Gent ( Site 1428) — Ghent

Denmark · 1 center

• Rigshospitalet-Department of paediatrics and adolescent medicine, Section of Paed haem-onc — Copenhagen

Greece · 1 center

• Aghia Sophia Children's Hospital-First Department of Pediatrics, National and Kapodistrian — Athens

Hungary · 1 center

• Semmelweis Egyetem ( Site 1838) — Budapest

Netherlands · 1 center

• Prinses Maxima Centrum voor Kinderoncologie ( Site 1510) — Utrecht

Slovakia · 1 center

• Narodny ustav detskych chorob ( Site 1592) — Bratislava

Sweden · 1 center

• Sahlgrenska Universitetssjukhuset ( Site 1634) — Gothenburg

Taiwan · 1 center

• National Taiwan University Hospital ( Site 1983) — Taipei

Identifiers

NCT: NCT06395103 · 9999-01A · MK-9999-01A · LIGHTBEAM-U01 · 2023-507178-41-00 · U1111-1295-3459 · jRCT2031250824

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗