Clinical trial NCT06941272: A Study of Patritumab Deruxtecan in Pediatric Participants With Relapsed or Refractory Solid Tumors (MK-9999-01C/LIGHTBEAM-U01)
Official title: LIGHTBEAM-U01 Substudy 01C: A Phase 1/2 Substudy to Evaluate the Safety and Efficacy of Patritumab Deruxtecan in Pediatric Participants With Relapsed or Refractory Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Malignant Neoplasm
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2025-04-23
Enrollment: 50
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Researchers are looking for new ways to treat children with hepatoblastoma or rhabdomyosarcoma (RMS) that has relapsed or is refractory:

* Hepatoblastoma is a common liver cancer in babies and very young children
* RMS is a cancer that starts in muscle cells, often in a child's head and neck, bladder, arms, or legs
* Relapsed means the cancer came back after treatment
* Refractory means the cancer did not respond (get smaller or go away) to treatment

The study treatment HER3-DXd (also known as MK-1022 or patritumab 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 HER3-DXd in children and if they tolerate it
* What happens to HER3-DXd in children's bodies over time
* If children who receive HER3-DXd have the cancer get smaller or go away

Detailed description: This study will have 2 parts: a safety lead-in to demonstrate a tolerable safety profile and confirm a preliminary recommended phase 2 dose (RP2D) (Part 1) followed by an efficacy evaluation (Part 2).

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

* Has one of the following histologically confirmed advanced or metastatic solid tumors: Rhabdomyosarcoma (RMS), or Hepatoblastoma
* Has progressed after at least 1 prior systemic treatment for RMS or hepatoblastoma and who has no satisfactory alternative treatment option (ie, is ineligible for other standard treatment regimens)
* Participants who have adverse events (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
* Hepatitis B surface antigen (HBsAg) positive participants are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load
* Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable

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

* Has a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids or has current ILD/pneumonitis, and/or suspected ILD/pneumonitis that cannot be ruled out by standard diagnostic assessments
* Has clinically severe respiratory compromise resulting from intercurrent pulmonary illness
* Has a history of solid organ transplant
* Has a history of allogeneic stem cell transplant
* Has clinically significant corneal disease
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis/leptomeningeal disease; participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression) for at least 4 weeks
* Has uncontrolled or significant cardiovascular disorder
* Has a history of clinically significant congenital cardiac syndrome
* Has a history of human immunodeficiency virus (HIV) infection
* Has a known additional malignancy that is progressing or has required active treatment within the past 1 year
* Has an active infection requiring systemic therapy
* Has concurrent active hepatitis B (HBsAg positive and/or detectable HBV deoxyribonucleic acid \[DNA\]) and HCV defined as anti-HCV antibody (Ab) positive and detectable HCV ribonucleic acid \[RNA\]) infection
* Has not adequately recovered from major surgery or have ongoing surgical complications

Primary outcomes:
measure: Part 1: Percentage of Participants Who Experience Dose-limiting Toxicities (DLTs)
timeFrame: Cycle 1 (up to approximately 21 days); each cycle is 21 days
measure: Part 1: Percentage of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to approximately 5 years
measure: Part 1: Percentage of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 5 years
measure: Part 1: Area Under the Curve (AUC) of total anti-HER3 antibody liquid chromatography-mass spectrometry (LC-MS) in plasma
timeFrame: At designated timepoints (up to approximately 5 years)
measure: Part 1: AUC of anti-HER3 antibody-conjugated DXd (anti-HER3-ac-DXd) in plasma
timeFrame: At designated timepoints (up to approximately 5 years)
measure: Part 1: AUC of DXd in plasma
timeFrame: At designated timepoints (up to approximately 5 years)
measure: Part 1: Maximum Concentration (Cmax) of anti-HER3 antibody LC-MS in plasma
timeFrame: At designated timepoints (up to approximately 5 years)
measure: Part 1: Cmax of anti-HER3-ac-DXd in plasma
timeFrame: At designated timepoints (up to approximately 5 years)
measure: Part 1: Cmax of DXd in plasma
timeFrame: At designated timepoints (up to approximately 5 years)
measure: Part 1: Concentration Immediately Before the Next Dose is Administered (Ctrough) of anti-HER3 antibody LC-MS in plasma
timeFrame: At designated timepoints (up to approximately 5 years)
measure: Part 1: Ctrough of anti-HER3-ac-DXd
timeFrame: At designated timepoints (up to approximately 5 years)
measure: Part 1: Ctrough of DXd in plasma
timeFrame: At designated timepoints (up to approximately 5 years)
measure: Part 1 and Part 2: Objective Response Rate (ORR)
timeFrame: Up to approximately 5 years
Secondary outcomes:
measure: Part 2: Percentage of Participants Who Experience an AE
timeFrame: Up to approximately 5 years
measure: Part 2: Percentage of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 5 years
measure: Part 1 and Part 2: Disease Control Rate (DCR)
timeFrame: Up to approximately 5 years
measure: Part 1 and Part 2: Time to Response (TTR)
timeFrame: Up to approximately 5 years
measure: Part 1 and Part 2: Duration of Response (DOR)
timeFrame: Up to approximately 5 years
measure: Part 1 and Part 2: Progression-free Survival (PFS)
timeFrame: Up to approximately 5 years
measure: Part 1 and Part 2: Overall Survival (OS)
timeFrame: Up to approximately 5 years
measure: Part 2: AUC of total anti-HER3 antibody LC-MS in plasma
timeFrame: At designated timepoints (up to approximately 5 years)
measure: Part 2: AUC of anti-HER3-ac-DXd in plasma
timeFrame: At designated timepoints (up to approximately 5 years)
measure: Part 2: AUC of DXd in plasma
timeFrame: At designated timepoints (up to approximately 5 years)
measure: Part 2: Cmax of anti-HER3 antibody LC-MS in plasma
timeFrame: At designated timepoints (up to approximately 5 years)
measure: Part 2: Cmax of anti-HER3-ac-DXd in plasma
timeFrame: At designated timepoints (up to approximately 5 years)
measure: Part 2: Cmax of DXd in plasma
timeFrame: At designated timepoints (up to approximately 5 years)
measure: Part 2: Ctrough of anti-HER3 antibody LC-MS in plasma
timeFrame: At designated timepoints (up to approximately 5 years)
measure: Part 2: Ctrough of anti-HER3-ac-DXd in plasma
timeFrame: At designated timepoints (up to approximately 5 years)
measure: Part 2: Ctrough of DXd in plasma
timeFrame: At designated timepoints (up to approximately 5 years)
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa Health Care Holden Comprehensive Cancer Center
state: Iowa
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital-Pediatrics
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: