A Randomized Phase II Study to Evaluate the Safety and Efficacy of Trastuzumab Deruxtecan Versus CDK4/6 Inhibitor-based Endocrine Therapy as First-line Therapy of HR-positive and HER2-low/Ultralow Advanced Breast Cancer Patients Classified as Non-luminal Subtype According to Gene Expression Profiling.
概览
- 阶段
- 2 期
- 干预措施
- Trastuzumab deruxtecan (T-DXd, DS-8201a)
- 疾病 / 适应症
- 未指定
- 发起方
- MedSIR
- 入组人数
- 200
- 试验地点
- 69
- 主要终点
- Progression-free survival (PFS)
- 状态
- 招募中
- 最后更新
- 2个月前
概览
简要总结
This trial studies a type of advanced breast cancer defined as hormone receptor HR-positive/HER2-negative and classified as non-luminal by gene expression profiling (PAM50). Patients will be treated with trastuzumab deruxtecan (T-DXd) or with physician's choice of CDK4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET). The main purpose of the study is to analyze the efficacy of T-DXd in patients who have HR-positive and HER2-low/ultralow advanced breast cancer classified as non-luminal subtype.
详细描述
This is an international, multicenter, two-arm, randomized, phase II clinical trial for patients with unresectable locally recurrent or metastatic HR-positive and HER2-low/ultralow breast cancer classified as non-luminal by gene expression profiling. Female or male patients ≥ 18 years of age with HR-positive and HER2-low/ultralow locally recurrent inoperable or metastatic breast cancer classified as non-luminal subtype by central PAM50 analysis will be enrolled. Patients will be randomized to T-DXd 5.4 mg/kg body weight administered as an IV infusion on Day 1 of each 21-day cycle or physician's choice of CDK4/6 inhibitor plus endocrine therapy. The main objective of the study is to demonstrate that first-line T-DXd compared with CDK4/6i plus ET is superior in prolonging the progression free survival (PFS) based on investigator assessment in patients with HR-positive, HER2-low advanced breast cancer classified as non-luminal by central PAM50 analysis (HER2-low population) and all patients.
研究者
Alicia García
Scientific
Medica Scientia Innovation Research S.L.
入排标准
入选标准
- •Patients must be capable to understand the purpose of the study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.
- •Female or male patients ≥ 18 years of age at the time of signing ICF.
- •ECOG performance status of 0-
- •Minimum life expectancy of ≥ 12 weeks at screening.
- •Evidence of HER2-low expression (1+ by immunohistochemistry (IHC) or 2+ and negative by an in situ hybridization \[ISH\] test) or HER2-ultralow (IHC 0 with faint membrane staining and in ≤ 10% of tumor cells) breast cancer according to the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines determined by a MEDSIR's designated central laboratory, using Ventana 4B5 antibody. This assessment has to be done on the most recently available (archived or newly collected) formalin-fixed, paraffin-embedded (FFPE) tumor tissue blocks (≤ 6 weeks or FFPE of a tumor sample obtained after last prior systemic therapy) from core or excisional biopsy from a locally recurrent (breast or locoregional lymph nodes) or metastatic tumor lesion, excluding bone metastases.
- •Non-luminal breast cancer subtype as per central PAM50 analysis determined in the most recently available (archived or newly collected) FFPE tumor tissue blocks (≤ 6 weeks or FFPE of a tumor sample obtained after last prior systemic therapy) from core or excisional biopsy from a locally recurrent (breast or locoregional lymph nodes) or metastatic tumor lesion with the exception of bone metastases.
- •Patients must have HR-positive (estrogen receptor \[ER\] and/or progesterone receptor \[PgR\]-positive defined as ≥ 1% positive stained cells) status according to the most recent ASCO/CAP guidelines locally determined prior to study entry.
- •Unresectable locally recurrent or metastatic breast cancer documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.
- •Evaluable disease according to RECIST v.1.
- •Patients with bone-only disease are not allowed. Patients with bone metastases with soft tissue masses measuring \> 10 mm are eligible.
排除标准
- •Current participation in another therapeutic clinical trial, except other translational studies.
- •Treatment with approved or investigational cancer therapy within 3 weeks prior to initiation of study drug.
- •Treatment with chloroquine/hydroxychloroquine within 14 days prior to initiation of study drug.
- •Have previously been treated with T-DXd and/or fulvestrant. Note: patients who experienced relapse after more than 1 year from completion of fulvestrant are eligible.
- •Note I: previous treatment with anti-HER2 therapies in (neo-) adjuvant setting will be allowed for participants who showed conversion from HER2-positive expression in primary breast tumor sample to HER2-low or HER2-ultralow expression (HER2 loss) in relapsed tumor sample.
- •Patients with advanced, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions \[pleural, pericardial, and/or peritoneal\] and pulmonary lymphangitis).
- •Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of CDK4/6i, such as history of GI surgery which may result in intestinal blind loops and patients with clinically significant gastroparesis, short bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel disease, or diarrhea of CTCAE Grade \>
- •Known central nervous system (CNS) involvement (brain metastases and/or leptomeningeal carcinomatosis). Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy.
- •Have a concurrent malignancy or malignancy within 5 years of study enrollment with the exception of carcinoma in situ of the cervix and basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor's Medical Monitor is required.
- •Known allergy or hypersensitivity reaction to any of the investigational medicinal products (IMPs) or their inactive ingredients.
研究组 & 干预措施
Arm A
干预措施: Trastuzumab deruxtecan (T-DXd, DS-8201a)
Arm B
干预措施: CDK4/6i plus ET
结局指标
主要结局
Progression-free survival (PFS)
时间窗: Up to 25 months
PFS, defined as the period from randomization date to the first occurrence of documented radiographic disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1. in HER2-low patients.
次要结局
- Overall survival (OS)(Up to 25 months)
- Objective response rate (ORR)(Up to 25 months)
- Clinical benefit rate (CBR)(Up to 25 months)
- Duration of response (DoR)(Up to 25 months)
- Time to response (TTR)(Up to 25 months)
- Time to treatment failure (TTF)(Up to 25 months)
- Time to first subsequent chemotherapy (TFSC)(Up to 25 months)
- Progression free survival 2 (PFS2)(Up to 25 months)
- Time to start of first subsequent therapy or death (TFST)(Up to 25 months)
- Best percentage of change in tumor burden(Up to 25 months)
- Health-related quality-of-life (HRQoL)(Up to 25 months)
- Incidence of Adverse Events, Serious Adverse Events and Suspected Unexpected Serious Adverse Reactions(Up to 25 months)