A Phase 3b, Multicenter, Global, Interventional, Open-label Study of Trastuzumab Deruxtecan (T-DXd), an Anti-HER2-Antibody Drug Conjugate (ADC), in Subjects Who Have Unresectable and/or Metastatic HER2-low or HER2 Immunohistochemistry (IHC) 0 Breast Cancer (DESTINY-Breast15)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 250
- 试验地点
- 169
- 主要终点
- Time From the Start of T-DXd to Initiation of Subsequent Anticancer Treatment (TTNT)
研究概览
简要总结
This study will evaluate the safety and efficacy of trastuzumab deruxtecan (T-DXd) in participants with human epidermal growth factor receptor 2 (HER2)-low or HER2 immunohistochemistry (IHC) 0 (who are both hormone receptor [HR]-negative and HR-positive) unresectable and/or metastatic breast cancer.
详细描述
The primary endpoint of interest in this study is time to next treatment (TTNT), a measure that will determine how long T-DXd allows patients to derive clinical benefit from the study drug.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Sign and date the main informed consent form
- •Must agree to provide a newly obtained or archival baseline biopsy from primary and/or metastatic lesion.
- •Pathologically documented Breast Cancer (BC) tumor
- •Is unresectable and/or metastatic.
- •Is hormone receptor-negative or hormone receptor-positive.
- •Must include percentage of positively stained cells to characterize if hormone receptor-positive or -negative.
- •Has confirmed HER2 IHC 1+ or IHC 2+/ISH- (HER2-low) status or HER2 IHC 0 status as determined according to ASCO CAP 2018 guidelines1 based on sample collected during Tissue Screening as described above.
- •Was never previously HER2-positive (IHC 3+ or IHC 2+/ISH+) on prior pathology testing (per ASCO CAP guidelines).
- •Was never previously treated with anti-HER2 therapy in the metastatic setting.
- •Has had at least one and up to two prior lines of therapy in the metastatic setting.
- •In participants with hormone receptor-positive HER2-low metastatic BC (Cohort 3):
- •Has recurrent disease <2 years from the initiation of adjuvant ET OR
- •Has disease progression on CDK4/6 inhibitor-based regimen within 12 months of completion of adjuvant therapy with a CDK4/6 inhibitor OR
- •Has disease progression within the first 12 months of CDK4/6 in the first line metastatic setting
- •Presence of at least one measurable lesion based on computed tomography or magnetic resonance imaging.
- •Participants with brain metastases are allowed in the study. The brain lesion(s) should be small (<2 cm), untreated, asymptomatic, not requiring urgent medical intervention, and are asymptomatic and clinically stable.
- •Has an Eastern Cooperative Oncology Group performance status of 0 or
- •Has a minimum life expectancy of 12 weeks at Screening.
- •Has a left ventricular ejection fraction ≥50% within 28 days before enrollment.
- •Has adequate organ and bone marrow function within 28 days before enrollment.
- •Has adequate treatment washout period before enrollment.
- •Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception.
排除标准
- •Prior treatment with an antibody drug conjugate (ADC).
- •Uncontrolled or significant cardiovascular disease.
- •Has a corrected QT interval prolongation.
- •Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
- •Has spinal cord compression or clinically active central nervous system metastases.
- •Has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, other solid tumors curatively treated, or contralateral BC.
- •Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
- •Has a history of severe hypersensitivity reactions to other monoclonal antibodies.
- •Has an uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals.
- •Active primary immunodeficiency, known uncontrolled active human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
- •Has history of receiving a live, attenuated vaccine (messenger RNA and replication-deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study drug.
- •Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline.
- •Is pregnant or breastfeeding or planning to become pregnant.
- •Lung-specific intercurrent clinically significant illnesses.
- •Any autoimmune, connective tissue, or inflammatory disorders.
- •Prior complete pneumonectomy.
研究组 & 干预措施
Cohort 2: HR-negative, HER2 IHC 0
Participants with HR-negative HER2 IHC 0 unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd.
干预措施: Trastuzumab Deruxtecan (Drug)
Cohort 1: HR-negative, HER2-low
Participants with HR-negative HER2-low unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd.
干预措施: Trastuzumab Deruxtecan (Drug)
Cohort 3: HR-positive, HER2-low
Participants with HR-positive HER2-low unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd.
Participants must also have recurrent disease <2 years from the initiation of adjuvant ET or have disease progression on CDK4/6 inhibitor-based regimen within 12 months of completion of adjuvant therapy with a CDK4/6 inhibitor or have disease progression within the first 12 months of CDK4/6 in the first line metastatic setting.
干预措施: Trastuzumab Deruxtecan (Drug)
Cohort 4: HR-positive, HER2 IHC 0
Participants with HR-positive HER2 IHC 0 unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd.
干预措施: Trastuzumab Deruxtecan (Drug)
结局指标
主要结局
Time From the Start of T-DXd to Initiation of Subsequent Anticancer Treatment (TTNT)
时间窗: Until subsequent therapy or death, assessed up to 24 months
TTNT is defined as the time interval from the date of first dose of T-DXd to the initiation of the next anticancer treatment or death due to any cause.
次要结局
- Time From Start of T-DXd to Discontinuation of T-DXd or Death (TTD)(Until treatment discontinuation or death, up to 24 months)
- Objective Response Rate (ORR)(Until progression, assessed up to 24 months)
- Time to First and Definitive Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ) Scales(Assessed up to 24 months)
- Time to First and Definitive Deterioration in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS)(Assessed up to 24 months)
- Patient's Global Impression of Change (PGI-C) Response(Assessed up to 24 months)
- Mean Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ)-BR45 Score(Assessed up to 24 months)
- Real-World Progression Free Survival (PFS)(Until progression or death, assessed up to 24 months)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Up to follow up period, up to 24 months)
- Mean Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ)-C30 Score(Assessed up to 24 months)
- Patient's Global Impression of Treatment Tolerability (PGI-TT) Response(Assessed up to 24 months)
- Mean Change from Baseline in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L)(Assessed up to 24 months)
- Mean Change From Baseline in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L) Index Score(Assessed up to 24 months)
- Mean Change From Baseline in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS)(Assessed up to 24 months)
- Patient's Global Impression of Severity (PGI-S) Response(Assessed up to 24 months)