A Phase 1b/2 Multicentre, Open-label, Modular, Dose-finding and Dose-expansion Study to Explore the Safety, Tolerability, and Anti-tumour Activity of Trastuzumab Deruxtecan (T-DXd) in Combination With Other Anti-cancer Agents in Patients With HER2-positive Metastatic Breast Cancer (DESTINY-Breast07)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 245
- 试验地点
- 1
- 主要终点
- Occurrence of adverse events (AEs)- Part 1
研究概览
简要总结
DESTINY-Breast07 will investigate the safety, tolerability, and anti-tumour activity of trastuzumab deruxtecan (T-DXd) in combination with other anti-cancer agents in patients with HER2-positive Metastatic Breast Cancer
详细描述
This study is modular in design allowing assessment of safety, tolerability and anti-tumour activity of T-DXd in combination with other anti-cancer agents. Combination-treatment modules will have 2 parts: a dose-finding phase (Part 1), and a dose expansion phase (Part 2); the recommended Phase 2 dose (RP2D) determined in Part 1 will be used for the dose-expansion in Part 2.
The target population of interest in this study is patients with HER2-positive (as per ASCO/CAP 2018 guidelines) advanced/MBC inclusive of patients with active and stable brain metastases. Part 1 of each module will enroll patients with locally assessed HER2-positive advanced/MBC in second-line or later patients. Part 2 of each module will enroll patients with locally assessed HER2-positive breast cancer who have not received prior treatment for advanced/metastatic disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Patients must be at least 18 years of age
- •Pathologically documented breast cancer that:
- •Is advanced/unresectable (patients that can be treated with curative intent are not eligible) or metastatic
- •HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local assessment. The local HER2 result must be from a tumour sample obtained in the metastatic setting.
- •Is documented as hormone receptor-positive (estrogen or progesterone receptor) or negative in the metastatic setting
- •Patient must have adequate tumor sample from the metastatic setting for biomarker assessment
- •ECOG Performance Status of 0 or 1
- •Disease progression on or after the last systemic therapy prior to starting study treatment
- •At least 1 prior treatment line in metastatic setting required.
- •Part 2 (Modules 0 - 5)
- •a) No prior lines of therapy for advanced/MBC allowed
- •Part 2 (Module 6 and 7) a) Zero or one prior lines of therapy for advanced/MBC allowed
- •CNS Inclusion
- •Modules 0 - 5 Patients must have no brain metastases or stable brain metastases.
- •Module 6 and 7 Patients must have untreated brain metastases not needing local therapy or previously treated brain metastases that have progressed since prior local therapy
排除标准
- •Uncontrolled or significant cardiovascular disease
- •Active or prior documented (non-infectious) ILD/pneumonitis that required steroids, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
- •Lung-specific intercurrent clinically significant illnesses
- •Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- •Spinal cord compression or a history of leptomeningeal carcinomatosis
- •Prior treatment with immune checkpoint inhibitors
- •Prior treatment with an ADC containing a topoisomerase I inhibitor
- •Prior treatment with tucatinib
- •CNS Exclusion
- •Modules 0 - 5: Has untreated brain metastasis
- •Module 6 and 7: Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg dexamethasone or any brain lesion thought to require immediate local therapy
研究组 & 干预措施
Module 2- T-DXd and Pertuzumab
T-DXd and Pertuzumab
干预措施: Trastuzumab deruxtecan (Drug)
Module 4- T-DXd and Durvalumab and Paclitaxel
T-DXd and Durvalumab and Paclitaxel (Arm not initiated in Part 1 and Part 2)
干预措施: Paclitaxel (Drug)
Module 0- T-DXd
T-DXd
干预措施: Trastuzumab deruxtecan (Drug)
Module 1- T-DXd and Durvalumab
T-DXd and Durvalumab
干预措施: Trastuzumab deruxtecan (Drug)
Module 1- T-DXd and Durvalumab
T-DXd and Durvalumab
干预措施: Durvalumab (Drug)
Module 2- T-DXd and Pertuzumab
T-DXd and Pertuzumab
干预措施: Pertuzumab (Drug)
Module 3- T-DXd and Paclitaxel
T-DXd and Paclitaxel (Arm not initiated in Part 2)
干预措施: Trastuzumab deruxtecan (Drug)
Module 3- T-DXd and Paclitaxel
T-DXd and Paclitaxel (Arm not initiated in Part 2)
干预措施: Paclitaxel (Drug)
Module 4- T-DXd and Durvalumab and Paclitaxel
T-DXd and Durvalumab and Paclitaxel (Arm not initiated in Part 1 and Part 2)
干预措施: Trastuzumab deruxtecan (Drug)
Module 4- T-DXd and Durvalumab and Paclitaxel
T-DXd and Durvalumab and Paclitaxel (Arm not initiated in Part 1 and Part 2)
干预措施: Durvalumab (Drug)
Module 5 - T-DXd and Tucatanib
T-DXd and tucatinib (Arm not initiated in Part 2)
干预措施: Trastuzumab deruxtecan (Drug)
Module 5 - T-DXd and Tucatanib
T-DXd and tucatinib (Arm not initiated in Part 2)
干预措施: Tucatinib (Drug)
Module 6 - T-DXd and Tucatinib
T-DXd and tucatinib in patients with active brain metastases (Part 2 Only) (Arm not initiated)
干预措施: Trastuzumab deruxtecan (Drug)
Module 6 - T-DXd and Tucatinib
T-DXd and tucatinib in patients with active brain metastases (Part 2 Only) (Arm not initiated)
干预措施: Tucatinib (Drug)
Module 7 - T-DXd
T-DXd monotherapy in patients with active brain metastases (Part 2 Only)
干预措施: Trastuzumab deruxtecan (Drug)
结局指标
主要结局
Occurrence of adverse events (AEs)- Part 1
时间窗: Up to follow-up period, approximately 53 months
Occurrence of AEs in Part 1 graded according to NCI CTCAE v5.0
Occurrence of serious adverse events (SAEs)- Part 1
时间窗: Up to follow-up period, approximately 53 months
Occurrence of SAEs in Part 1 graded according to NCI CTCAE v5.0
Occurrence of adverse events (AEs)- Part 2
时间窗: Up to follow-up period, approximately 53 months
Occurrence of AEs in Part 2 graded according to NCI CTCAE v5.0
Occurrence of serious adverse events (SAEs)- Part 2
时间窗: Up to follow-up period, approximately 53 months
Occurrence of SAEs in Part 2 graded according to NCI CTCAE v5.0
次要结局
- Progression Free Survival 2 (PFS2)- Part 2(Assessed up to approximately 53 months)
- Serum Concentration of Trastuzumab Deruxtecan (T-DXd)(While on study drug up to study completion, approximately 53 months)
- Serum Concentration of Durvalumab(While on study drug up to study completion, approximately 53 months)
- Serum Concentration of Pertuzumab(While on study drug up to study completion, approximately 53 months)
- Plasma Concentration of Paclitaxel(While on study drug up to study completion, approximately 53 months)
- Immunogenicity of Pertuzumab(Up to follow-up period, approximately 53 months)
- Progression Free Survival (PFS)- Part 1 and Part 2(Until progression, assessed up to approximately 53 months)
- Duration of Response (DoR)- Part 2(Until progression, assessed up to approximately 53 months)
- Overall Survival (OS)- Part 2(Until death, assessed up to approximately 53 months)
- Objective Response Rate (ORR)- Part 1 and Part 2(Until progression, assessed up to approximately 53 months)
- Immunogenicity of trastuzumab deruxtecan(Up to follow-up period, approximately 53 months)
- Immunogenicity of Durvalumab(Up to follow-up period, approximately 53 months)
- Plasma Concentration of Tucatinib(While on study drug up to study completion, approximately 53 months)