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

Официальное название

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

Обзор

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.

Вмешательства

• Биопрепарат Zilovertamab vedotin
  Administered via IV infusion

Первичные конечные точки

• Part 1: Number of Participants from 1 to <18 years of Age Who Experience a Dose-Limiting Toxicity (DLT) [Срок оценки: Up to 42 days]
• Part 1: Number of Participants from 1 to <18 years of Age Who Experience One or More Adverse Events (AEs) [Срок оценки: Up to approximately 54 months]
• Part 1: Number of Participants from 1 to <18 years of Age Who Discontinue Study Treatment Due to AEs [Срок оценки: Up to approximately 54 months]
• Part 1: Number of Participants from 1 to <18 years of Age Who Receive Dose Modification Due to AEs [Срок оценки: Up to approximately 54 months]
• Part 1 and Part 2: Objective Response (OR) for Participants with B-Cell Acute Lymphoblastic Leukemia (B-ALL) [Срок оценки: 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 [Срок оценки: Up to approximately 54 months]

Вторичные конечные точки (12)

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

Критерии участия

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

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 17 центров

• 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
• … и ещё 9 центров

Франция · 5 центров

• 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

Великобритания · 5 центров

• 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

Бразилия · 4 центра

• 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

Германия · 4 центра

• 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

Испания · 4 центра

• 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

Австралия · 3 центра

• 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

Канада · 3 центра

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

Чили · 3 центра

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

Колумбия · 3 центра

• 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

Италия · 3 центра

• 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 центра

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

Чехия · 2 центра

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

Израиль · 2 центра

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

South Korea · 2 центра

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

Бельгия · 1 центр

• UZ Gent ( Site 1428) — Ghent

Дания · 1 центр

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

Греция · 1 центр

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

Венгрия · 1 центр

• Semmelweis Egyetem ( Site 1838) — Budapest

Нидерланды · 1 центр

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

Словакия · 1 центр

• Narodny ustav detskych chorob ( Site 1592) — Bratislava

Швеция · 1 центр

• Sahlgrenska Universitetssjukhuset ( Site 1634) — Gothenburg

Тайвань · 1 центр

• National Taiwan University Hospital ( Site 1983) — Taipei

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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