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
- 1/2 期
- 状态
- 进行中（未招募）
- 入组人数
- 46
- 试验地点
- 11
- 主要终点
- Part 1: AEs, SAEs, DLTs, laboratory findings
研究概览
简要总结
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. 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.
Part 1: To assess the safety and tolerability, and determine RP2D for the T-DXd combinations Part 2: To assess the safety and tolerability of T-DXd monotherapy and T-DXd combinations
研究设计
- 分配方式
- Randomized
- 主要目的
- Part 2
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Patients must be at least 18 years of age
- •Pathologically documented breast cancer that: a) Is advanced/unresectable (patients that can be treated with curative intent are not eligible) or metastatic b) 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. c) 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
- •Part 1 a) Disease progression on or after the last systemic therapy prior to starting study treatment b) 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
- •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
结局指标
主要结局
Part 1: AEs, SAEs, DLTs, laboratory findings
Part 1: AEs, SAEs, DLTs, laboratory findings
Part 2: AEs, SAEs, laboratory findings
Part 2: AEs, SAEs, laboratory findings
次要结局
- Part 1 and Part 2: ORR is defined as the proportion of patients who have a CR or PR, as determined by the Investigator at local site per RECIST 1.1.
- Part 1 and Part 2: PFS is defined as time from the date of randomisation until the date of progression as assessed by the Investigator at local site per RECIST 1.1, or death due to any cause.
- Part 2: PFS2 is defined as time from the date of randomisation until the date of progression on next line treatment (the earliest of the progression event subsequent to first subsequent anticancer therapy) or death; second progression will be defined according to local standard clinical practice.
- Part 2: DoR is defined as time from the date of first documented response until the date of documented progression or death in the absence of disease progression.
- Part 2: OS is defined as time from the date of randomisation until the date of death due to any cause.
- Serum concentration of T-DXd, total anti-HER2 antibody, MAAA- 1181a, durvalumab, and pertuzumab; plasma concentration of paclitaxel and tucatinib
- Immunogenicity for T-DXd, durvalumab, and pertuzumab
研究者
AstraZeneca Clinical Study Information Center
Scientific
AstraZeneca AB