HERTHENA-Breast-01: A Phase 1b/2, Multicenter, Open-label, Dose-Finding Study to Evaluate the Safety and Antitumor Activity of Patritumab Deruxtecan in Participants With HER2 Positive Unresectable Locally Advanced Breast Cancer or Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 81
- 试验地点
- 22
- 主要终点
- Number of Participants Experiencing Dose-Limiting Toxicity (DLT)
研究概览
简要总结
Researchers want to learn if patritumab deruxtecan (MK-1022) can treat certain breast cancers. The breast cancers being studied are HER2 positive unresectable locally advanced or metastatic (the cancer has spread to other parts of the body). The goals of this study are to learn:
- About the safety and how well people tolerate of patritumab deruxtecan
- How many people have the cancer respond (get smaller or go away) to treatment
详细描述
The following countries will be participating in the trial: Canada, United Kingdom, Israel, Japan, South Korea, and USA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 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 histologically confirmed HER2+ locally advanced unresectable breast cancer or metastatic breast cancer
- •Human immunodeficiency virus (HIV)-infected participants must have well-controlled HIV on antiretroviral therapy (ART)
- •Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable hepatitis B virus (HBV) viral load before allocation
- •Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 within 7 days before start of study intervention
- •Has received at least a minimum of 2 and a maximum of 5 prior lines of anti-HER2 therapy in the locally advanced or metastatic setting
- •Had disease progression on or after any previous trastuzumab deruxtecan (T-DXd) treatment
- •Has received no more than 5 prior lines of anti-HER2 therapy in the locally advanced or metastatic setting
- •Has received and had disease progression from T-DXd treatment in any setting and a maximum of 3 prior lines of anti-HER2 therapy in the locally advanced or metastatic setting. T-DXd must be the most recent therapy received before enrollment.
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Uncontrolled or significant cardiovascular disease
- •History of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/interstitial lung disease
- •Has clinically severe respiratory compromise
- •Has any history of or evidence of any current leptomeningeal disease
- •Has clinically significant corneal disease
- •Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection
- •HIV infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Known additional malignancy that is progressing or has required active treatment within the past 3 years
- •Evidence of spinal cord compression or brain metastases
- •Has an active infection requiring systemic therapy
- •Concurrent active HBV and HCV infection
- •Has had major surgical procedure (excluding placement of vascular access) less than 28 days
- •- Has received prior treatment with tucatinib, lapatinib, or neratinib, or any investigational HER2-targeted tyrosine kinase inhibitors in the locally advanced or metastatic setting
研究组 & 干预措施
Patritumab deruxtecan plus pertuzumab and trastuzumab
Participants receive patritumab deruxtecan IV infusion, pertuzumab IV infusion, and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision.
干预措施: Trastuzumab (Biological)
Patritumab deruxtecan plus trastuzumab
Participants receive patritumab deruxtecan intravenous (IV) infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision.
干预措施: Patritumab deruxtecan (Biological)
Patritumab deruxtecan plus trastuzumab and tucatinib
Participants receive patritumab deruxtecan IV infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks), and tucatinib is administered orally twice daily for each 21-day cycle, until disease progression, intolerable toxicity, or investigator decision.
干预措施: Trastuzumab (Biological)
Patritumab deruxtecan plus trastuzumab and tucatinib
Participants receive patritumab deruxtecan IV infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks), and tucatinib is administered orally twice daily for each 21-day cycle, until disease progression, intolerable toxicity, or investigator decision.
干预措施: Trastuzumab Biosimilar (Biological)
Patritumab deruxtecan plus trastuzumab and tucatinib
Participants receive patritumab deruxtecan IV infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks), and tucatinib is administered orally twice daily for each 21-day cycle, until disease progression, intolerable toxicity, or investigator decision.
干预措施: Tucatinib (Biological)
Patritumab deruxtecan plus trastuzumab
Participants receive patritumab deruxtecan intravenous (IV) infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision.
干预措施: Trastuzumab (Biological)
Patritumab deruxtecan plus trastuzumab
Participants receive patritumab deruxtecan intravenous (IV) infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision.
干预措施: Trastuzumab Biosimilar (Biological)
Patritumab deruxtecan plus pertuzumab and trastuzumab
Participants receive patritumab deruxtecan IV infusion, pertuzumab IV infusion, and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision.
干预措施: Patritumab deruxtecan (Biological)
Patritumab deruxtecan plus pertuzumab and trastuzumab
Participants receive patritumab deruxtecan IV infusion, pertuzumab IV infusion, and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision.
干预措施: Trastuzumab Biosimilar (Biological)
Patritumab deruxtecan plus pertuzumab and trastuzumab
Participants receive patritumab deruxtecan IV infusion, pertuzumab IV infusion, and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision.
干预措施: Pertuzumab (Biological)
Patritumab deruxtecan plus trastuzumab and tucatinib
Participants receive patritumab deruxtecan IV infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks), and tucatinib is administered orally twice daily for each 21-day cycle, until disease progression, intolerable toxicity, or investigator decision.
干预措施: Patritumab deruxtecan (Biological)
结局指标
主要结局
Number of Participants Experiencing Dose-Limiting Toxicity (DLT)
时间窗: Up to 21 days
DLT will be defined as any drug-related AE observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle. The number of participants who experience a DLT will be presented.
Number of Participants with One or More Adverse Events (AEs)
时间窗: Up to approximately 13 months
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience an AE will be presented.
Number of Participants who Discontinue Study Intervention Due to an AE
时间窗: Up to approximately 12 months
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study treatment due to an AE will be presented.
次要结局
- Trough Concentration (Ctrough) of Total Patritumab Deruxtecan ADA(At designated time points (up to ~13 months))
- Area Under the Plasma Concentration-Time Curve (AUC) of Total Patritumab Deruxtecan ADA(At designated time points (up to ~13 months))
- Maximum Plasma Concentration (Cmax) of Patritumab Deruxtecan Antibody-Drug Conjugate (ADC)(At designated time points (up to ~13 months))
- Trough Concentration (Ctrough) of Patritumab Deruxtecan ADC(At designated time points (up to ~13 months))
- Area Under the Plasma Concentration-Time Curve (AUC) of Patritumab Deruxtecan ADC(At designated time points (up to ~13 months))
- Maximum Plasma Concentration (Cmax) of Total Patritumab Deruxtecan Antidrug Antibody (ADA)(At designated time points (up to ~13 months))
- Maximum Plasma Concentration (Cmax) of Patritumab Deruxtecan Free Payload(At designated time points (up to ~13 months))
- Trough Concentration (Ctrough) of Patritumab Deruxtecan Free Payload(At designated time points (up to ~13 months))
- Area Under the Plasma Concentration-Time Curve (AUC) of Patritumab Deruxtecan Free Payload(At designated time points (up to ~13 months))