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

Phase 2Not Yet RecruitingNCT07630974

Merck Sharp & Dohme LLC134 enrolled

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

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

134

Conditions

Malignant Neoplasm

Interventions

Eligibility

Sex: ALLMin age: 1 MonthMax age: 17 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Part 1: Number of Participants From ≥1 Month to <12 Years Who Experience a Dose-limiting Toxicity (DLT)

A DLT is any of a prespecified list of adverse events (AEs) that occur during Cycle 1 (up to 21 days) if attributed to the study treatment and not attributed to any other clearly identifiable cause. The percentage of participants who experience DLTs will be reported. Each cycle is 21 days.

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)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experience AEs will be reported.

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)

ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experience CR or PR as assessed by the investigator will be presented.

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)

DCS-4 is defined as no occurrence of disease progression per disease specific criteria as assessed by investigator or death due to any cause by Month 4 following the first administration of study intervention for participants with OST. Participants who discontinue from study for any reason prior to completing the third post baseline (or at least 16 weeks) response assessments will be considered disease control failures.

Time frame: Up to 4 Months

Secondary Outcomes

Part 1 and Part 2: Duration of Response (DOR) For Participants With NBL, RMS, WT, or OST

For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death. PD is defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions is also considered PD. DOR as assessed by the investigator will be presented.

Time frame: Up to approximately 5 years

Part 1 and Part 2: Disease Control Rate (DCR) For Participants With NBL, RMS, WT, or OST

DCR is defined, per RECIST 1.1, as the percentage of participants who have a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) or Stable Disease (SD). SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm). Note: The appearance of one or more new lesions is also considered PD. The time from the first dose until the date of SD must be greater than or equal to 6 weeks. The DCR as assessed by the investigator will be presented.

Time frame: Up to approximately 5 years

Part 1 and Part 2: Time to Response (TTR) For Participants With NBL, RMS, WT, or OST

For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, TTR is defined as the time from the first dose to the first documented evidence of a CR or PR. The TTR as assessed by the investigator will be presented.

Time frame: Up to approximately 5 years

Part 1 and Part 2: Progression-free Survival (PFS) For Participants With NBL, RMS, WT, or OST

PFS is defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first as assessed by RECIST 1.1. PD is defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions is also considered PD. PFS as assessed by the investigator will be presented.

Part 1 and Part 2: ORR For participants with OST

ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants with OST who experience CR or PR as assessed by the investigator will be presented.

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: Area under the concentration time curve from Time 0 to the End of the Dosing Period (AUCtau) of I-Dxd

Blood samples will be collected at specified intervals to determine the 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

Blood samples will be collected at specified intervals to determine the Ctrough of I-Dxd.

Time frame: At designated timepoints (up to approximately 5 years)

Part 1 and Part 2: Maximum Plasma Concentration (Cmax) of released drug payload (Dxd)

Blood samples will be collected at specified intervals to determine the Cmax of 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 Dxd

Blood samples will be collected at specified intervals to determine the AUCtau of Dxd.

Time frame: At designated timepoints (up to approximately 5 years)

Part 1 and Part 2: Number of Participants with antidrug antibodies (ADA) against I-Dxd

Blood samples will be collected at specified intervals to assess I-Dxd immunogenicity by determining the incidence of ADA of I-Dxd.

Time frame: At designated timepoints (up to approximately 5 years)