A Study of Ifinatamab Deruxtecan in Pediatric Participants With Relapsed or Refractory Solid Tumors (MK-9999-01D/LIGHTBEAM-U01)

Официальное название

LIGHTBEAM-U01 Substudy 01D: A Phase 1b/2 Substudy to Evaluate the Safety and Efficacy of Ifinatamab Deruxtecan in Pediatric Participants With Relapsed or Refractory Solid Tumors

Обзор

Researchers are looking for new ways to treat children with relapsed or refractory solid tumors: * Relapsed means the cancer came back after treatment * Refractory means the cancer did not respond (get smaller or go away) to treatment * Solid tumors are cancers mostly in body organs and tissues, not in the blood or other body liquids The study treatment I-DXd (also known as MK-2400 or ifinatamab deruxtecan) is an antibody-drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. The goals of this study are to learn: * About the safety of I-DXd and if children younger than 12 years old tolerate it * How many children who receive I-DXd have the cancer get smaller or go away

Подробное описание

This study will have 2 parts: Part 1 will evaluate the safety and tolerability and determine the recommended dose for expansion (RDE) of I-DXd, followed by Part 2 an efficacy expansion.

Вмешательства

• Биопрепарат Ifinatamab Deruxtecan
  IV infusion

Первичные конечные точки

• Part 1: Number of Participants From ≥1 Month to <12 Years Who Experience a Dose-limiting Toxicity (DLT) [Срок оценки: Cycle 1 (up to approximately 21 days); each cycle is 21 days]
• Part 1: Number of Participants From ≥1 Month to <12 Years Who Experience One or More Adverse Events (AEs) [Срок оценки: Up to approximately 5 years]
• Part 1: Number of Participants From ≥1 Month to <12 Years Who Discontinue Study Intervention Due to an AE [Срок оценки: Up to approximately 5 years]
• Part 1: Number of Participants From ≥1 Month to <12 Years Who Receive Dose Modifications Due to AEs [Срок оценки: Up to approximately 5 years]
• Part 1 and Part 2: Objective Response Rate (ORR) for Participants with neuroblastoma (NBL), rhabdomyosarcoma (RMS), and Wilms tumor (WT) [Срок оценки: Up to approximately 5 years]
• Part 1 and Part 2: Disease Control Success at 4 Months (DCS-4) for Participants with osteosarcoma (OST) [Срок оценки: Up to 4 Months]

Вторичные конечные точки (12)

• Part 1 and Part 2: Duration of Response (DOR) For Participants With NBL, RMS, WT, or OST [Срок оценки: Up to approximately 5 years]
• Part 1 and Part 2: Disease Control Rate (DCR) For Participants With NBL, RMS, WT, or OST [Срок оценки: Up to approximately 5 years]
• Part 1 and Part 2: Time to Response (TTR) For Participants With NBL, RMS, WT, or OST [Срок оценки: Up to approximately 5 years]
• Part 1 and Part 2: Progression-free Survival (PFS) For Participants With NBL, RMS, WT, or OST [Срок оценки: Up to approximately 5 years]
• Part 1 and Part 2: ORR For participants with OST [Срок оценки: Up to approximately 5 years]
• Part 1 and Part 2: Overall Survival (OS) [Срок оценки: Up to approximately 5 years]
• Part 1 and Part 2: Number of Participants With NBL, RMS, WT, or OST Who Experience an AE [Срок оценки: Up to approximately 5 years]
• Part 1 and Part 2: Number of Participants With NBL, RMS, WT, or OST Who Discontinue Study Treatment Due to an AE [Срок оценки: Up to approximately 5 years]
• Part 1 and Part 2: Number of Participants With NBL, RMS, WT, or OST Who Receive Dose Modification Due to an AE [Срок оценки: Up to approximately 5 years]
• Part 1 and Part 2: Maximum Plasma Concentration (Cmax) of I-Dxd [Срок оценки: At designated timepoints (up to approximately 5 years)]
• Part 1 and Part 2: Area under the concentration time curve from Time 0 to the End of the Dosing Period (AUCtau) of I-Dxd [Срок оценки: At designated timepoints (up to approximately 5 years)]
• Part 1 and Part 2: Plasma Trough Concentration (Ctrough) of I-Dxd [Срок оценки: At designated timepoints (up to approximately 5 years)]

Критерии участия

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

• In Part 1, participant has recurrent or relapsed, refractory solid tumors (excluding primary central nervous system (CNS)); and in Part 2, participant has recurrent or relapsed, refractory and histologically confirmed diagnosis of osteosarcoma (OST), neuroblastoma (NBL), rhabdomyosarcoma (RMS), or Wilms tumor (WT). All participants must meet the following criteria: Has documented radiological disease progression after at least 1 line of prior therapy in the locally advanced/metastatic setting and who has no satisfactory alternative treatment option (ie, is ineligible for other standard treatment regimens).
• Is an individual of any sex/gender, ≥1 month to <12 years of age for Part 1 and ≥1 month to <18 years for Part 2 at the time of providing the informed consent or assent, as applicable
• Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible.

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

• Has clinically significant corneal disease
• Has a history of cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event within 6 months before screening
• Has uncontrolled or significant cardiovascular disease, including conduction abnormalities, hypertension, ischemic heart disease, heart failure, and peripheral vascular disease
• Has any history of interstitial lung disease (ILD)/pneumonitis, irrespective of steroid use, except for a history of radiation pneumonitis that did not require steroids, current ILD, or Clinical or radiographic suspicion of ILD for which the diagnosis of ILD cannot be ruled out
• Has clinically severe respiratory compromise resulting from intercurrent pulmonary illnesses
• Has an active, known or suspected autoimmune disease.
• Has history of solid organ transplant.
• Has history of allogeneic stem cell transplant (SCT).
• Has known active CNS metastases and/or carcinomatous meningitis/leptomeningeal disease/spinal cord compression. Participants with untreated and asymptomatic brain metastases or previously treated brain metastases may participate provided they are radiologically stable, (i.e, without evidence of progression) for at least 4 weeks
• Has history of human immunodeficiency virus (HIV) infection.
• Has known additional malignancy that is progressing or has required active treatment within the past 1 year.
• Has active infection requiring systemic therapy
• Has known hypersensitivity or contraindication to either the study intervention substance or inactive ingredients in the study intervention product
• 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 · 7 центров

• University of Iowa Hospitals ( Site 4017) — Iowa City
• Dana Farber Cancer Center ( Site 4013) — Boston
• Rutgers Cancer Institute of New Jersey ( Site 4008) — New Brunswick
• Memorial Sloan Kettering Cancer Center ( Site 4010) — New York
• New York Medical College ( Site 4023) — Valhalla
• Children's Hospital of Philadelphia (CHOP) ( Site 4021) — Philadelphia
• Intermountain - Primary Children's Hospital ( Site 4014) — Salt Lake City

Испания · 3 центра

• Hospital Sant Joan de Déu ( Site 4717) — Esplugues de Llobregat
• Hospital Niño Jesús ( Site 4715) — Madrid
• Hospital Universitari Vall d Hebron ( Site 4716) — Barcelona

Израиль · 2 центра

• Rambam Health Care Campus ( Site 4674) — Haifa
• Sheba Medical Center ( Site 4675) — Ramat Gan

South Korea · 2 центра

• Seoul National University Hospital-Pediatrics ( Site 4972) — Seoul
• Asan Medical Center-Pediatrics - Pedicatric Oncology ( Site 4973) — Seoul

Бельгия · 1 центр

• UZ Gent ( Site 4428) — Ghent

Дания · 1 центр

• Rigshospitalet ( Site 4467) — Copenhagen

Франция · 1 центр

• CENTRE LEON BERARD ( Site 4100) — Lyon

Швеция · 1 центр

• Sahlgrenska Universitetssjukhuset ( Site 4634) — Gothenburg

Идентификаторы

NCT: NCT07630974 · 9999-01D · U1111-1322-6561 · 2025-522339-32-00 · LIGHTBEAM-U01 · MK-9999-01D

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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