An Open-label, Randomized, Phase 3 Study to Evaluate Patritumab Deruxtecan Monotherapy Versus Treatment of Physician's Choice in Hormone Receptor-positive, HER2-negative Unresectable Locally Advanced or Metastatic Breast Cancer (HERTHENA-Breast04).
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,000
- 试验地点
- 199
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
Researchers are looking for other ways to treat breast cancer (BC) that is hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) and either unresectable locally advanced or metastatic.
- HR positive (HR+) means the cancer cells have proteins that attach to estrogen or progesterone (hormones) which help the cancer to grow and spread
- HER2 negative (HER2-) means the cancer cells have a low amount of a protein called HER2
- Unresectable locally advanced means the cancer cannot be completely removed by surgery and has spread into nearby tissue or muscles
- Metastatic means the cancer has spread to other parts of the body
Treatment for this type of breast cancer usually includes endocrine therapy (ET) and sometimes a second treatment. The main goal of this study is to learn if people who receive patritumab deruxtecan (also known as HER3-DXd and MK-1022) live longer overall or without the cancer growing/spreading, compared to people who receive chemotherapy or a different drug called trastuzumab deruxtecan.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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 a diagnosis of hormone receptor positive (HR+)/human epidermal growth factor receptor 2 (HER2)- invasive breast carcinoma that is either locally advanced disease not amenable to resection with curative intent (herein called unresectable) or metastatic disease not treatable with curative intent
- •Has centrally-confirmed HR+ and HER2- results and human epidermal growth factor receptor 3 (HER3) evaluable results from a biopsy obtained from a distant metastatic site or a locally advanced lesion on or after the most recent line of therapy (with certain exceptions)
- •Must have had progression or recurrence on prior cyclin-dependent kinase (CDK)4/6 inhibitor + endocrine therapy (ET) with one of the following:
- •Radiographic disease progression, as assessed by the investigator, on CDK4/6 inhibitor + ET as 1L for treatment of unresectable locally advanced or metastatic HR+/HER2- breast cancer. CDK4/6 inhibitor + ET must be the only line of therapy received in the advanced setting, or
- •Disease recurrence, either radiographic and/or confirmed histologically via biopsy as assessed by the investigator, while on adjuvant ET in combination with a CDK4/6 inhibitor OR within 24 months from the date of last dose of adjuvant CDK4/6 inhibitor
- •Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
- •Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy
- •Has an Eastern Cooperative Oncology Group performance status of 0 or 1 assessed within 7 days before randomization
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Has breast cancer amenable to treatment with curative intent
- •Is eligible to receive additional endocrine-based treatment in the advanced setting as determined by the investigator
- •Has a known germline breast cancer gene (BRCA) mutation (deleterious or suspected deleterious) where poly (ADP-ribose) polymerase (PARP) inhibitor(s) is a potential treatment option
- •Has current visceral crisis or is at risk for impending visceral crisis that has or may cause imminent organ compromise and/or other life-threatening complications
- •Has any of the following: a pulse oximeter reading <92% at rest, or requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
- •Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
- •Has ≥Grade 2 peripheral neuropathy.
- •Has clinically significant corneal disease
- •Has received prior chemotherapy for unresectable locally advanced or metastatic breast cancer
- •Has received prior treatment with an anti-HER3 antibody and/or antibody-drug conjugate that consists of a topoisomerase I inhibitor (eg, T-DXd) or any other topoisomerase I inhibitor therapy
- •Has received prior systemic anticancer therapy within 4 weeks (or 5 half-lives, whichever is shorter) before randomization; participants previously treated with ET plus a CDK4/6 inhibitor may participate as long as at least 2 weeks have elapsed since the last dose of therapy was administered
- •Has received prior radiotherapy for non-central nervous system disease, or required corticosteroids for radiation-related toxicities, within 14 days of the first dose of study intervention
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
- •Has known additional malignancy that is progressing or has required active treatment within the past 3 years
- •Has history of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids, has current pneumonitis/interstitial lung disease, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening
- •Has severe hypersensitivity (≥Grade 3) to HER3-DXd and/or any of its excipients
- •Has severe hypersensitivity (≥Grade 3) to all the available TPC and/or any of their excipients
研究组 & 干预措施
Treatment of Physician's Choice
Participants receive treatment of physician's choice (TPC) for up to 13 months. The TPC may be any of the following options: Paclitaxel (80 mg/m^2) on Days 1, 8, 15, and 22 of each 4-week cycle; Paclitaxel (90 mg/m^2) on Days 1, 8, and 15 of each 4-week cycle; Nab-paclitaxel (100 mg/m^2) on Days 1, 8, and 15 of each 4-week cycle; Capecitabine (1000 mg/m^2) bid on Days 1 to 14 of each 3-week cycle; Liposomal doxorubicin (50 mg/m^2) on Day 1 of each 4-week cycle; or trastuzumab deruxtecan (T-DXd) (5.4 mg/kg) Q3W.
干预措施: Trastuzumab deruxtecan (Biological)
Treatment of Physician's Choice
Participants receive treatment of physician's choice (TPC) for up to 13 months. The TPC may be any of the following options: Paclitaxel (80 mg/m^2) on Days 1, 8, 15, and 22 of each 4-week cycle; Paclitaxel (90 mg/m^2) on Days 1, 8, and 15 of each 4-week cycle; Nab-paclitaxel (100 mg/m^2) on Days 1, 8, and 15 of each 4-week cycle; Capecitabine (1000 mg/m^2) bid on Days 1 to 14 of each 3-week cycle; Liposomal doxorubicin (50 mg/m^2) on Day 1 of each 4-week cycle; or trastuzumab deruxtecan (T-DXd) (5.4 mg/kg) Q3W.
干预措施: Paclitaxel (Drug)
Treatment of Physician's Choice
Participants receive treatment of physician's choice (TPC) for up to 13 months. The TPC may be any of the following options: Paclitaxel (80 mg/m^2) on Days 1, 8, 15, and 22 of each 4-week cycle; Paclitaxel (90 mg/m^2) on Days 1, 8, and 15 of each 4-week cycle; Nab-paclitaxel (100 mg/m^2) on Days 1, 8, and 15 of each 4-week cycle; Capecitabine (1000 mg/m^2) bid on Days 1 to 14 of each 3-week cycle; Liposomal doxorubicin (50 mg/m^2) on Day 1 of each 4-week cycle; or trastuzumab deruxtecan (T-DXd) (5.4 mg/kg) Q3W.
干预措施: Nab-paclitaxel (Drug)
Patritumab Deruxtecan
Participants receive patritumab deruxtecan via intravenous (IV) infusion every 3 weeks (Q3W) for approximately 13 months.
干预措施: Patritumab deruxtecan (Biological)
Treatment of Physician's Choice
Participants receive treatment of physician's choice (TPC) for up to 13 months. The TPC may be any of the following options: Paclitaxel (80 mg/m^2) on Days 1, 8, 15, and 22 of each 4-week cycle; Paclitaxel (90 mg/m^2) on Days 1, 8, and 15 of each 4-week cycle; Nab-paclitaxel (100 mg/m^2) on Days 1, 8, and 15 of each 4-week cycle; Capecitabine (1000 mg/m^2) bid on Days 1 to 14 of each 3-week cycle; Liposomal doxorubicin (50 mg/m^2) on Day 1 of each 4-week cycle; or trastuzumab deruxtecan (T-DXd) (5.4 mg/kg) Q3W.
干预措施: Capecitabine (Drug)
Treatment of Physician's Choice
Participants receive treatment of physician's choice (TPC) for up to 13 months. The TPC may be any of the following options: Paclitaxel (80 mg/m^2) on Days 1, 8, 15, and 22 of each 4-week cycle; Paclitaxel (90 mg/m^2) on Days 1, 8, and 15 of each 4-week cycle; Nab-paclitaxel (100 mg/m^2) on Days 1, 8, and 15 of each 4-week cycle; Capecitabine (1000 mg/m^2) bid on Days 1 to 14 of each 3-week cycle; Liposomal doxorubicin (50 mg/m^2) on Day 1 of each 4-week cycle; or trastuzumab deruxtecan (T-DXd) (5.4 mg/kg) Q3W.
干预措施: Liposomal doxorubicin (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Up to approximately 45 months
PFS is defined as the time from first day of study intervention to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by blinded independent central review (BICR). Per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.
Progression Free Survival (PFS)
时间窗: Up to approximately 45 months
PFS is defined as the time from first day of study intervention to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by blinded independent central review (BICR). Per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.
Overall Survival (OS)
时间窗: Up to approximately 85 months
OS is the length of time from when the participant starts treatment until death from any cause.
次要结局
- Objective Response Rate (ORR)(Up to approximately 85 months)
- Duration of Response (DOR)(Up to approximately 85 months)
- Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score(Baseline and up to approximately 85 months)
- Change from Baseline in the EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score(Baseline and up to approximately 85 months)
- Change from Baseline in the EORTC-QLQ-C30 Emotional Functioning (Items 1-5) Combined Score(Baseline and up to approximately 85 months)
- Change from Baseline in the EORTC-QLQ-C30 Pain (Items 9 and 19) Combined Score(Baseline and up to approximately 85 months)
- Time to First Deterioration (TTD) in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score(Baseline and up to approximately 85 months)
- TTD in the EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score(Baseline and up to approximately 85 months)
- TTD in the EORTC-QLQ-C30 Emotional Functioning (Items 1-5) Combined Score(Baseline and up to approximately 85 months)
- Number of Participants Who Experience One or More Adverse Event (AEs)(Up to approximately 85 months)
- Number of Participants Who Discontinue Study Treatment Due to an AE(Up to approximately 85 months)
- Objective Response Rate (ORR)(Up to approximately 85 months)
- Duration of Response (DOR)(Up to approximately 85 months)
- Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score(Baseline and up to approximately 85 months)
- Change from Baseline in the EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score(Baseline and up to approximately 85 months)
- Change from Baseline in the EORTC-QLQ-C30 Emotional Functioning (Items 1-5) Combined Score(Baseline and up to approximately 85 months)
- Change from Baseline in the EORTC-QLQ-C30 Pain (Items 9 and 19) Combined Score(Baseline and up to approximately 85 months)
- Time to First Deterioration (TTD) in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score(Baseline and up to approximately 85 months)
- TTD in the EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score(Baseline and up to approximately 85 months)
- TTD in the EORTC-QLQ-C30 Emotional Functioning (Items 1-5) Combined Score(Baseline and up to approximately 85 months)
- TTD in the EORTC-QLQ-C30 Pain (Items 9 and 19) Combined Score(Baseline and up to approximately 85 months)
- Number of Participants Who Experience One or More Adverse Event (AEs)(Up to approximately 85 months)
- Number of Participants Who Discontinue Study Treatment Due to an AE(Up to approximately 85 months)