A Multicenter, Prospective Phase II Single-arm Study Evaluating the Efficacy and Safety of Neoadjuvant Treatment with T-DXd in Combination with an Immune Checkpoint Inhibitor in HR-positive HER2 Low-expressing Chinese Patients with Early-stage Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 23
- 主要终点
- pathologic complete remission
研究概览
简要总结
This is a prospective, open-label, multicenter, single-arm clinical study designed to compare the efficacy and safety of neoadjuvant treatment with T-DXd in combination with an immune checkpoint inhibitor in patients with primary intermediate- to high-risk HR-positive, HER2-overexpressing early-stage breast cancer.
详细描述
Neoadjuvant therapy, a systemic therapy administered prior to localized treatments such as surgery, has become a key component in the management of non-metastatic breast cancer. Neoadjuvant chemotherapy is often used to treat early-stage, high-risk hormone receptor-positive (HR+) breast cancer; however, the rate of pathological complete remission(pCR) is only 5-8 %. Moreover, neoadjuvant chemotherapy has significant toxicity, with approximately 25-40% of patients discontinuing chemotherapy or reducing their dosage due to side effect.
Much evidence suggests that immune checkpoint inhibitors (ICIs) combined with chemotherapy significantly increase pCR rates in HR+ breast cancer.
The CheckMate 7FL study evaluated the efficacy of ICI (nabulizumab) in early-stage HR-positive breast cancer, and ICI in combination with chemotherapy increased the pCR rate to 24%, compared to 13.8% in the chemotherapy arm[4].
The Keynote756 clinical trial demonstrated for the first time that the addition of an ICI (pembrolizumab) to a neoadjuvant chemotherapy regimen for early-stage, high-risk ER+/HER2- breast cancer significantly increased patients' pCR rates. These clinical trials imply that ICIs in combination with chemotherapy can provide more benefit to patients with early-stage breast cancer compared to traditional neoadjuvant chemotherapy treatments.
Trastuzumab deruxtecan (DS-8201a, T-DXd) is a novel HER2-targeted antibody-drug coupling (ADC) approved by the FDA and NMPA for the treatment of HER2-positive and HER2-low expressing metastatic breast cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Adults between the ages of 18 and 70 at the time of signing the informed consent form.
- •An Eastern Cooperative Oncology Group (ECOG) score of 0 to
- •Previously untreated, operable invasive breast cancer measuring greater than 2.0 centimeters (cT2) with positive clinical lymph nodes (cN1/cN2); or clinically staged T3-T4, clinically lymph node-negative (N0) or clinically lymph node-positive (cN1/cN2) without distal metastases.
- •Tumors with low levels of HER2 expression by immunohistochemistry (IHC), defined as IHC 1+ or IHC 2+ and FISH negative.
- •Tumor documented as HR-positive (ER and/or PgR-positive [ER or PgR ≥1%] by local assessment according to ASCO-CAP guidelines).
- •Patients who agree to undergo surgical treatment for breast cancer when they meet surgical criteria after neoadjuvant therapy.
排除标准
- •Stage IV (metastatic) breast cancer and bilateral breast cancer
- •Previous history of invasive breast cancer.
- •Previous history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS)
- •Other malignant tumors within 5 years, excluding cured carcinoma in situ of the cervix and non-melanoma skin cancers.
研究组 & 干预措施
T-DXd combined with immune checkpoint inhibitor
干预措施: T-DXd combined with immune checkpoint inhibitor (Drug)
结局指标
主要结局
pathologic complete remission
时间窗: 3 years
次要结局
- overall survival(3 years)
- event free survival(3 years)
- invasive disease free survival(3 years)
研究者
Huijin Wang
Director of Thyroid and Breast Disease Center
Guangzhou Women and Children's Medical Center