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

Official title

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

Overview

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

Detailed description

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.

Interventions

• Biological Ifinatamab Deruxtecan
  IV infusion

Primary outcome measures

• Part 1: Number of Participants From ≥1 Month to <12 Years Who Experience a Dose-limiting Toxicity (DLT) [Time frame: 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) [Time frame: Up to approximately 5 years]
• Part 1: Number of Participants From ≥1 Month to <12 Years Who Discontinue Study Intervention Due to an AE [Time frame: Up to approximately 5 years]
• Part 1: Number of Participants From ≥1 Month to <12 Years Who Receive Dose Modifications Due to AEs [Time frame: 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) [Time frame: Up to approximately 5 years]
• Part 1 and Part 2: Disease Control Success at 4 Months (DCS-4) for Participants with osteosarcoma (OST) [Time frame: Up to 4 Months]

Secondary outcome measures (12)

• Part 1 and Part 2: Duration of Response (DOR) For Participants With NBL, RMS, WT, or OST [Time frame: Up to approximately 5 years]
• Part 1 and Part 2: Disease Control Rate (DCR) For Participants With NBL, RMS, WT, or OST [Time frame: Up to approximately 5 years]
• Part 1 and Part 2: Time to Response (TTR) For Participants With NBL, RMS, WT, or OST [Time frame: Up to approximately 5 years]
• Part 1 and Part 2: Progression-free Survival (PFS) For Participants With NBL, RMS, WT, or OST [Time frame: Up to approximately 5 years]
• Part 1 and Part 2: ORR For participants with OST [Time frame: Up to approximately 5 years]
• Part 1 and Part 2: Overall Survival (OS) [Time frame: Up to approximately 5 years]
• Part 1 and Part 2: Number of Participants With NBL, RMS, WT, or OST Who Experience an AE [Time frame: 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 [Time frame: 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 [Time frame: Up to approximately 5 years]
• Part 1 and Part 2: Maximum Plasma Concentration (Cmax) of I-Dxd [Time frame: 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 [Time frame: At designated timepoints (up to approximately 5 years)]
• Part 1 and Part 2: Plasma Trough Concentration (Ctrough) of I-Dxd [Time frame: At designated timepoints (up to approximately 5 years)]

Eligibility criteria

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

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 · 7 centers

• 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

Spain · 3 centers

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

Israel · 2 centers

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

South Korea · 2 centers

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

Belgium · 1 center

• UZ Gent ( Site 4428) — Ghent

Denmark · 1 center

• Rigshospitalet ( Site 4467) — Copenhagen

France · 1 center

• CENTRE LEON BERARD ( Site 4100) — Lyon

Sweden · 1 center

• Sahlgrenska Universitetssjukhuset ( Site 4634) — Gothenburg

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗