A Phase 3, Randomized, Multi-center, Open-label Study of Trastuzumab Deruxtecan (T-DXd) Versus Investigator's Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Breast Cancer Patients Whose Disease Has Progressed on Endocrine Therapy in the Metastatic Setting (DESTINY-Breast06)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 866
- 试验地点
- 293
- 主要终点
- Progression-Free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2 (HER2)-Low Population
研究概览
简要总结
This study will evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy in human epidermal growth factor receptor (HER)2-low, hormone receptor (HR) positive breast cancer patients whose disease has progressed on endocrine therapy in the metastatic setting.
详细描述
Eligible patients will be those patients who have had disease progression on at least 2 previous lines of endocrine therapies given for the treatment of metastatic disease or disease progression within 6 months of starting first line treatment for metastatic disease with an endocrine therapy combined with a CDK4/6 inhibitor. All patients must have historically confirmed HR positive (either estrogen receptor and/or progesterone receptor positive), HER2-low (defined as IHC2+/ISH- and IHC 1+) or HER2 IHC >0 <1+ expression, as determined by central laboratory testing results, advanced or metastatic breast cancer.
The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy. This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy. This study is also looking to see how the treatment and the cancer affects patients' quality of life.
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
盲法说明
This study is an open-label study that will be conducted "Sponsor-blind". To maintain the integrity of the study, Sponsor personnel directly involved in study conduct will not undertake or have access to efficacy data aggregated by treatment group prior to final data readout for the primary endpoint.
入排标准
- 年龄范围
- 18 Years 至 105 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be ≥18 years of age
- •Pathologically documented breast cancer that:
- •is advanced or metastatic
- •has a history of HER2-low or negative expression by local test, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or HER2 IHC 0 (ISH- or untested)
- •has HER2-low or HER2 IHC >0 <1+ expression as determined by the central laboratory result established on a tissue sample taken in the metastatic setting
- •was never previously HER2-positive
- •is documented HR+ disease in the metastatic setting.
- •No prior chemotherapy for advanced or metastatic breast cancer.
- •Has adequate tumor samples for assessment of HER2 status
- •Must have either:
- •disease progression within 6 months of starting first line metastatic treatment with an endocrine therapy combined with a CDK4/6 inhibitor or
- •disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy in the metastatic setting. Of note with regards to the ≥2 lines of previous ET requirement: disease recurrence while on the first 24 months of starting adjuvant ET, will be considered a line of therapy; these patients will only require 1 line of ET in the metastatic setting.
- •Has protocol-defined adequate organ and bone marrow function
排除标准
- •Ineligible for all options in the investigator's choice chemotherapy arm
- •Lung-specific intercurrent clinically significant illnesses
- •Uncontrolled or significant cardiovascular disease or infection
- •Prior documented interstitial lung disease (ILD)/ pneumonitis that required steroids, current ILD/ pneumonitis, or suspected ILD/ pneumonitis that cannot be ruled out by imaging at screening.
- •Patients with spinal cord compression or clinically active central nervous system metastases
- •Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment
- •Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study during the follow up period of a prior interventional study (prescreening for this study while a patient is on treatment in another clinical study is acceptable)
研究组 & 干预措施
Trastuzumab deruxtecan
Trastuzumab deruxtecan (T-DXd; DS-8201a) arm
干预措施: Trastuzumab deruxtecan (Drug)
Standard of Care
Investigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm
干预措施: Capecitabine (Drug)
Standard of Care
Investigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm
干预措施: Paclitaxel (Drug)
Standard of Care
Investigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm
干预措施: Nab-Paclitaxel (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2 (HER2)-Low Population
时间窗: Response evaluations performed at screening, every 6 weeks (q6w) ± 1 week from randomization for 48 weeks, and then every 9 weeks (q9w) ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
PFS per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) assessed by BICR was defined as the time from the date of randomization until the date of PD, as defined or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions (TLs), taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 millimeter (mm) from nadir. Median PFS was calculated using Kaplan-Meier method and its confidence interval (CI) using Brookmeyer-Crowley method.
次要结局
- Overall Survival (OS) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population(From date of randomization until death due to any cause, up to PCD of 18 March 2024 (maximum of approximately 43.85 months))
- Progression-Free Survival Assessed by Blinded Independent Central Review in the Intent-to-Treat, Human Epidermal Growth Factor Receptor 2 Immunohistochemistry (IHC) >0 <1+ and Human Epidermal Growth Factor Receptor 2-low Population(Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months))
- Overall Survival (OS) in the Intent-to-Treat Population(From date of randomization until death due to any cause, up to PCD of 18 March 2024 (maximum of approximately 43.85 months))
- Progression-Free Survival Assessed by Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population(Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months))
- Objective Response Rate (ORR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population(Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months))
- Duration of Response (DOR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population(Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months))
- Objective Response Rate Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat and Human Epidermal Growth Factor Receptor 2 Immunohistochemistry >0 <1+ Population(Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months))
- Duration of Response Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat Population(Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months))
- Time From Randomization to Second Progression or Death (PFS2) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population(Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months))
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)(From first dose of study drug (Day 1) up to PCD of 18 March 2024 (maximum of approximately 43.85 months))
- Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a(Pre-dose on Day 1 of Cycles 1, 2, 4, 6 and 8; 15 minutes post-dose on Day 1 of Cycles 1, 2 and 4; and 5 hours post-dose on Day 1 of Cycle 1 (each cycle is 21 days))
- Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91(Baseline (Day 1) and Week 91)
- Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58(Baseline (Day 1) and Week 58)
- Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score(From randomization until date of first symptom deterioration that is confirmed, up to PCD of 18 March 2024 (maximum of approximately 43.85 months))
- Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab Deruxtecan(From Day 1 up to PCD of 18 March 2024 (maximum of approximately 43.85 months))
- Time to First Subsequent Treatment or Death (TFST) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population(From Day 1 up to 64 months)
- Time to Second Subsequent Treatment or Death (TSST) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population(From Day 1 up to 64 months)