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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 101
- 主要终点
- Part 1: Area Under the Curve (AUC) of total anti-HER3 antibody liquid chromatography-mass spectrometry (LC-MS) in plasma
研究概览
简要总结
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
详细描述
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Month 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •include but are not limited to the following:
- •Has a history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, or current ILD/pneumonitis, or suspected ILD/pneumonitis, or ILD that cannot be ruled out by imaging
- •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
研究组 & 干预措施
Patritumab Deruxtecan
Participants receive patritumab deruxtecan via IV infusion on Day 1 of each 3-week cycle until discontinuation or progression.
干预措施: Patritumab Deruxtecan (Biological)
结局指标
主要结局
Part 1: Area Under the Curve (AUC) of total anti-HER3 antibody liquid chromatography-mass spectrometry (LC-MS) in plasma
时间窗: At designated timepoints (up to approximately 5 years)
Blood samples will be collected at specified intervals for the determination of AUC.
Part 1: Percentage of Participants Who Experience Dose-limiting Toxicities (DLTs)
时间窗: 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)
时间窗: 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
时间窗: 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: AUC of anti-HER3 antibody-conjugated DXd (anti-HER3-ac-DXd) in plasma
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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.
次要结局
- Part 2: AUC of total anti-HER3 antibody LC-MS in plasma(At designated timepoints (up to approximately 5 years))
- Part 2: Percentage of Participants Who Experience an AE(Up to approximately 5 years)
- Part 2: Percentage of Participants Who Discontinue Study Treatment Due to an AE(Up to approximately 5 years)
- Part 1 and Part 2: Disease Control Rate (DCR)(Up to approximately 5 years)
- Part 1 and Part 2: Time to Response (TTR)(Up to approximately 5 years)
- Part 1 and Part 2: Duration of Response (DOR)(Up to approximately 5 years)
- Part 1 and Part 2: Progression-free Survival (PFS)(Up to approximately 5 years)
- Part 1 and Part 2: Overall Survival (OS)(Up to approximately 5 years)
- Part 2: AUC of anti-HER3-ac-DXd in plasma(At designated timepoints (up to approximately 5 years))
- Part 2: AUC of DXd in plasma(At designated timepoints (up to approximately 5 years))
- Part 2: Cmax of anti-HER3 antibody LC-MS in plasma(At designated timepoints (up to approximately 5 years))
- Part 2: Cmax of anti-HER3-ac-DXd in plasma(At designated timepoints (up to approximately 5 years))
- Part 2: Cmax of DXd in plasma(At designated timepoints (up to approximately 5 years))
- Part 2: Ctrough of anti-HER3 antibody LC-MS in plasma(At designated timepoints (up to approximately 5 years))
- Part 2: Ctrough of anti-HER3-ac-DXd in plasma(At designated timepoints (up to approximately 5 years))
- Part 2: Ctrough of DXd in plasma(At designated timepoints (up to approximately 5 years))