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

Phase 2RecruitingNCT06941272

Merck Sharp & Dohme LLC50 enrolled

Overview

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

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)

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Malignant Neoplasm

Interventions

Patritumab DeruxtecanBIOLOGICAL

IV Infusion

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: * 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. Participants with Grade ≤2 alopecia are also 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

Locations (48)

Children's Hospital Colorado-Center for Cancer and Blood Disorders ( Site 3016)

Aurora, Colorado, United States

RECRUITING

Johns Hopkins All Children's Hospital ( Site 3025)

St. Petersburg, Florida, United States

RECRUITING

University of Iowa Health Care Holden Comprehensive Cancer Center ( Site 3017)

Iowa City, Iowa, United States

RECRUITING

Corewell Health ( Site 3001)

Grand Rapids, Michigan, United States

Outcomes

Primary Outcomes

Part 1: Percentage of Participants Who Experience Dose-limiting Toxicities (DLTs)

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: Percentage of Participants Who Experience an Adverse Event (AE)

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: Percentage of Participants Who Discontinue Study Treatment Due to an AE

Time frame: Up to approximately 5 years

Part 1: Area Under the Curve (AUC) of total anti-HER3 antibody liquid chromatography-mass spectrometry (LC-MS) in plasma

Blood samples will be collected at specified intervals for the determination of AUC.

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

Part 1: AUC of anti-HER3 antibody-conjugated DXd (anti-HER3-ac-DXd) in plasma

Blood samples will be collected at specified intervals for the determination of AUC.

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

Part 1: AUC of DXd in plasma

Blood samples will be collected at specified intervals for the determination of AUC.

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

Part 1: Maximum Concentration (Cmax) of anti-HER3 antibody LC-MS in plasma

Blood samples will be collected at specified intervals for the determination of Cmax.

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

Part 1: Cmax of anti-HER3-ac-DXd in plasma

Blood samples will be collected at specified intervals for the determination of Cmax.

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

Part 1: Cmax of DXd in plasma

Blood samples will be collected at specified intervals for the determination of Cmax.

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

Part 1: Concentration Immediately Before the Next Dose is Administered (Ctrough) of anti-HER3 antibody LC-MS in plasma

Blood samples will be collected at specified intervals for the determination of Ctrough.

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

Part 1: Ctrough of anti-HER3-ac-DXd

Blood samples will be collected at specified intervals for the determination of Ctrough.

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

Part 1: Ctrough of DXd in plasma

Blood samples will be collected at specified intervals for the determination of Ctrough.

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

Part 1 and Part 2: Objective Response Rate (ORR)

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) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by the investigator will be presented.

Time frame: Up to approximately 5 years

Secondary Outcomes

Part 2: Percentage of Participants Who Experience an AE

Time frame: Up to approximately 5 years

Part 2: Percentage of Participants Who Discontinue Study Treatment Due to an AE

Time frame: Up to approximately 5 years

Part 1 and Part 2: Disease Control Rate (DCR)

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 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.

Central Contacts

Toll Free Number

CONTACT

1-888-577-8839 Trialsites@msd.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Children's Mercy Hospital ( Site 3024)

Kansas City, Missouri, United States

RECRUITING

Rutgers Cancer Institute of New Jersey ( Site 3008)

New Brunswick, New Jersey, United States

RECRUITING

New York Medical College ( Site 3023)

Valhalla, New York, United States

RECRUITING

Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 3003)

Fargo, North Dakota, United States

RECRUITING

Oregon Health and Science University ( Site 3004)

Portland, Oregon, United States

RECRUITING

Children's Hospital of Philadelphia (CHOP) ( Site 3021)

Philadelphia, Pennsylvania, United States

RECRUITING

...and 38 more locations

Time frame: Up to approximately 5 years

Part 1 and Part 2: Duration of Response (DOR)

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: Progression-free Survival (PFS)

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.

Time frame: Up to approximately 5 years

Part 1 and Part 2: Overall Survival (OS)

OS is defined as time from first dose of study treatment to death due to any cause.

Time frame: Up to approximately 5 years

Part 2: AUC of total anti-HER3 antibody LC-MS in plasma

Blood samples will be collected at specified intervals for the determination of AUC.

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

Part 2: AUC of anti-HER3-ac-DXd in plasma

Blood samples will be collected at specified intervals for the determination of AUC.

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

Part 2: AUC of DXd in plasma

Blood samples will be collected at specified intervals for the determination of AUC.

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

Part 2: Cmax of anti-HER3 antibody LC-MS in plasma

Blood samples will be collected at specified intervals for the determination of Cmax.

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

Part 2: Cmax of anti-HER3-ac-DXd in plasma

Blood samples will be collected at specified intervals for the determination of Cmax.

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

Part 2: Cmax of DXd in plasma

Blood samples will be collected at specified intervals for the determination of Cmax.

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

Part 2: Ctrough of anti-HER3 antibody LC-MS in plasma

Blood samples will be collected at specified intervals for the determination of Ctrough.

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

Part 2: Ctrough of anti-HER3-ac-DXd in plasma

Blood samples will be collected at specified intervals for the determination of Ctrough.

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

Part 2: Ctrough of DXd in plasma

Blood samples will be collected at specified intervals for the determination of Ctrough.

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