Malignant Neoplasm
Conditions
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)
Interventions
BIOLOGICALPatritumab Deruxtecan
IV Infusion
Sponsors
Merck Sharp & Dohme LLC
Daiichi Sankyo
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 17 Years
Healthy volunteers
No
Inclusion 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. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
Australia, Belgium, Brazil, Colombia, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Netherlands, Slovakia, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed