A Study of Patritumab Deruxtecan in Pediatric Participants With Relapsed or Refractory Solid Tumors (MK-9999-01C/LIGHTBEAM-U01)
- Registration Number
- NCT06941272
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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).
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Patritumab Deruxtecan Patritumab Deruxtecan Participants receive patritumab deruxtecan via IV infusion on Day 1 of each 3-week cycle until discontinuation or progression.
- Primary Outcome Measures
Name Time Method Part 1: Percentage of Participants Who Experience Dose-limiting Toxicities (DLTs) Cycle 1 (up to approximately 21 days); each cycle is 21 days 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.
Part 1: Percentage of Participants Who Experience an Adverse Event (AE) Up to approximately 5 years 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.
Part 1: Percentage of Participants Who Discontinue Study Treatment Due to an AE Up to approximately 5 years 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 discontinue study treatment due to an AE will be reported.
Part 1: Area Under the Curve (AUC) of total anti-HER3 antibody liquid chromatography-mass spectrometry (LC-MS) in plasma At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of AUC.
Part 1: AUC of anti-HER3 antibody-conjugated DXd (anti-HER3-ac-DXd) in plasma At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of AUC.
Part 1: AUC of DXd in plasma At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of AUC.
Part 1: Maximum Concentration (Cmax) of anti-HER3 antibody LC-MS in plasma At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of Cmax.
Part 1: Cmax of anti-HER3-ac-DXd in plasma At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of Cmax.
Part 1: Cmax of DXd in plasma At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of Cmax.
Part 1: Concentration Immediately Before the Next Dose is Administered (Ctrough) of anti-HER3 antibody LC-MS in plasma At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of Ctrough.
Part 1: Ctrough of anti-HER3-ac-DXd At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of Ctrough.
Part 1: Ctrough of DXd in plasma At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of Ctrough.
Part 1 and Part 2: Objective Response Rate (ORR) Up to approximately 5 years 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.
- Secondary Outcome Measures
Name Time Method Part 1 and Part 2: Progression-free Survival (PFS) Up to approximately 5 years 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: Overall Survival (OS) Up to approximately 5 years OS is defined as time from first dose of study treatment to death due to any cause.
Part 2: AUC of total anti-HER3 antibody LC-MS in plasma At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of AUC.
Part 2: AUC of anti-HER3-ac-DXd in plasma At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of AUC.
Part 2: AUC of DXd in plasma At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of AUC.
Part 2: Cmax of anti-HER3 antibody LC-MS in plasma At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of Cmax.
Part 2: Cmax of anti-HER3-ac-DXd in plasma At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of Cmax.
Part 2: Cmax of DXd in plasma At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of Cmax.
Part 2: Ctrough of anti-HER3 antibody LC-MS in plasma At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of Ctrough.
Part 2: Ctrough of anti-HER3-ac-DXd in plasma At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of Ctrough.
Part 2: Ctrough of DXd in plasma At designated timepoints (up to approximately 5 years) Blood samples will be collected at specified intervals for the determination of Ctrough.
Part 2: Percentage of Participants Who Experience an AE Up to approximately 5 years 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.
Part 2: Percentage of Participants Who Discontinue Study Treatment Due to an AE Up to approximately 5 years 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 discontinue study treatment due to an AE will be reported.
Part 1 and Part 2: Disease Control Rate (DCR) Up to approximately 5 years 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.
Part 1 and Part 2: Time to Response (TTR) Up to approximately 5 years 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.
Part 1 and Part 2: Duration of Response (DOR) Up to approximately 5 years 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.