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

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

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

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.

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