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Neoadjuvant Dalpiciclib + AI → SHR-A1811 for HR+/HER2-Low Breast Cancer (TD-DASHER-01)

2026年6月8日 更新者：Tang-Du Hospital

Dalpiciclib Combined With Aromatase Inhibitor (AI) Followed by SHR-A1811 as Neoadjuvant Therapy in Patients With Intermediate-to-High Risk HR+/HER2-Low Breast Cancer: A Phase II Exploratory Study

This is a phase II, single-arm, prospective exploratory study to evaluate the efficacy and safety of neoadjuvant dalpiciclib (a CDK4/6 inhibitor) plus an aromatase inhibitor (AI) followed by SHR-A1811 (an anti-HER2 antibody-drug conjugate) in patients with intermediate-to-high risk, hormone receptor-positive (HR+), HER2-low breast cancer. Patients will receive dalpiciclib (125 mg orally once daily, days 1-21, every 4 weeks) plus AI (anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg once daily) for 4 cycles, followed by SHR-A1811 (4.8 mg/kg intravenously every 3 weeks) for 4 cycles. The primary endpoint is objective response rate (ORR) per RECIST 1.1. Secondary endpoints include pathological complete response (pCR), breast-conserving surgery rate, event-free survival (EFS), change in Ki-67 index, and safety. A total of 20 participants will be enrolled.

研究概览

地位

尚未招聘

条件

干预/治疗

详细说明

This is a single-arm, open-label, phase II exploratory trial conducted at a single center (Second Affiliated Hospital of Air Force Medical University, China). The study aims to investigate the activity and safety of dalpiciclib plus an aromatase inhibitor (AI) followed by the HER2-directed antibody-drug conjugate (ADC) SHR-A1811 as neoadjuvant therapy for patients with intermediate-to-high risk, hormone receptor-positive (HR+), HER2-low breast cancer.

Preclinical evidence suggests that CDK4/6 inhibition may enhance the immunogenic cell death induced by ADCs and overcome tumor heterogeneity. Dalpiciclib is a selective CDK4/6 inhibitor with a distinct piperidine structure associated with low hepatotoxicity and minimal gastrointestinal side effects. SHR-A1811 is a HER2-targeted ADC composed of a humanized anti-HER2 IgG1 monoclonal antibody (based on trastuzumab sequence), a cleavable maleimide tetrapeptide (GGFG) linker, and a DNA topoisomerase I inhibitor (SHR169265). It demonstrates bystander killing of HER2-low cells. The 4-cycle induction with dalpiciclib plus AI prior to SHR-A1811 is designed to reduce tumor proliferation and potentially prime the tumor microenvironment before ADC administration.

Treatment administration

  • Dalpiciclib: 125 mg orally once daily on days 1-21 of each 28-day cycle (4 cycles total). Patients are instructed to take the tablet at approximately the same time each day, on an empty stomach (≥1 hour before or after food). Missed doses are not supplemented; vomiting within a short time after intake does not trigger a replacement dose. Interruption for >21 consecutive days requires study discontinuation. Dose reductions follow a stepwise scheme: 125 mg → 100 mg → 75 mg.
  • Aromatase inhibitor (AI): Investigator's choice of anastrozole 1 mg daily, letrozole 2.5 mg daily, or exemestane 25 mg daily, taken continuously during the first 4 cycles. Premenopausal patients (mandatory) and perimenopausal patients (at investigator's discretion) receive concomitant LHRH agonists (e.g., goserelin or leuprolide).
  • SHR-A1811: 4.8 mg/kg intravenously over a standard infusion duration on day 1 of each 21-day cycle (4 cycles total). The dose is recalculated based on body weight measured immediately before each cycle. If weight change from baseline is <10%, no dose adjustment is required. Dose reductions follow a 4.8 → 3.2 mg/kg step. Infusion-related reactions are managed according to a predefined algorithm (slow infusion, antihistamines, corticosteroids, or permanent discontinuation for grade ≥3 reactions).

研究类型

介入性

注册 (估计的)

20

阶段

  • 阶段2

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人
  • 年长者

接受健康志愿者

不

描述

Inclusion Criteria:

  1. Age ≥18 and ≤70 years
  2. Histologically confirmed invasive breast cancer, HR+ (ER ≥1% and/or PR ≥1%) and HER2-low (IHC 1+ or IHC 2+/ISH-)
  3. No prior systemic anti-tumor therapy for breast cancer
  4. Stage II-III (T1cN1-2M0, T2-4N0-2M0) per AJCC 8th edition

  5. At least one of the following intermediate-to-high risk factors:

    • Axillary lymph node involvement ≥1
    • Tumor size≥2 cm
    • Grade 3 tumor
    • Ki-67 ≥20%
  6. At least one measurable lesion per RECIST 1.1
  7. ECOG PS 0-1
  8. Adequate organ function (ANC ≥1.5×10⁹/L, platelets ≥100×10⁹/L, Hb ≥90 g/L, TBIL ≤1.5×ULN, ALT/AST ≤2.5×ULN, Cr ≤1.5×ULN or CrCl ≥60 mL/min, LVEF ≥50%, QTcF ≤470 ms in females, DLCO ≥50% predicted
  9. Negative pregnancy test (for women of childbearing potential) and agreement to use adequate contraception during and for 6 months after treatment
  10. Willing and able to provide informed consent and comply with study procedures

Exclusion Criteria:

  1. Non-pathologically confirmed breast cancer
  2. Bilateral, inflammatory, or occult breast cancer
  3. Prior anticancer therapy (chemotherapy, radiotherapy, targeted therapy, endocrine therapy, etc.)
  4. Concurrent use of other anticancer treatments
  5. Other malignancy within 5 years (except cured basal cell carcinoma or cervical carcinoma in situ)
  6. Participation in another interventional clinical trial within 4 weeks prior to first dose
  7. Use of immunosuppressive agents or systemic corticosteroids (>10 mg/day prednisone or equivalent) within 2 weeks prior to first dose
  8. Live or attenuated vaccine within 4 weeks prior to first dose
  9. Major surgery unrelated to breast cancer within 4 weeks prior to first dose
  10. Active or history of autoimmune disease requiring systemic treatment
  11. Known immunodeficiency (e.g., HIV positivity) or history of organ transplantation
  12. Uncontrolled or significant cardiovascular disease (e.g., NYHA class III/IV heart failure, myocardial infarction, unstable angina, arrhythmia requiring treatment, QTcF >470 ms, uncontrolled hypertension)
  13. Known or suspected interstitial lung disease (ILD) or significant pre-existing pulmonary disease
  14. Active hepatitis B (HBsAg positive and HBV DNA ≥500 IU/mL) or hepatitis C (HCV RNA above ULN), cirrhosis, or uncontrolled severe infection
  15. Known bleeding or thrombotic tendency
  16. Allergy or contraindication to any study drug or excipient
  17. Pregnancy, breastfeeding, or positive pregnancy test at baseline
  18. Any concurrent condition that may compromise patient safety or study compliance (e.g., uncontrolled hypertension, severe diabetes, active infection)
  19. History of neurological or psychiatric disorders (e.g., epilepsy, dementia) or any condition deemed unsuitable by the investigator.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：不适用
  • 介入模型：单组作业
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Dalpiciclib + Aromatase Inhibitor followed by SHR-A1811
药品：Dalpiciclib 125mg
CDK4/6 inhibitor, 125 mg oral tablet, taken once daily on days 1-21 of each 28 day cycle for 4 cycles.
药品：Aromatase Inhibitor
Includes anastrozole 1 mg/day, letrozole 2.5 mg/day, or exemestane 25 mg/day, administered orally once daily for 4 cycles.
药品：SHR-A1811
Anti-HER2 antibody-drug conjugate (ADC), 4.8 mg/kg intravenous infusion once every 3 weeks for 4 cycles

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Objective Response Rate (ORR)
大体时间：After completion of 8 cycles of neoadjuvant therapy (Cycles 1-4: 28 days/cycle; Cycles 5-8: 21 days/cycle), within 4 weeks prior to surgery
Proportion of patients achieving complete response (CR) or partial response (PR) per RECIST 1.1
After completion of 8 cycles of neoadjuvant therapy (Cycles 1-4: 28 days/cycle; Cycles 5-8: 21 days/cycle), within 4 weeks prior to surgery

次要结果测量

结果测量
措施说明
大体时间
Breast-Conserving Surgery Rate
大体时间：At the time of surgery
Proportion of participants who undergo breast-conserving surgery (BCS) after neoadjuvant therapy. BCS is defined as surgical resection of the primary tumor with negative margins while preserving the breast contour, as opposed to total mastectomy.
At the time of surgery
Event-Free Survival (EFS)
大体时间：From enrollment up to 5 years after last patient enrollment (assessed every 3 months during the first year, then every 6 months thereafter
EFS is defined as the time from enrollment to the first occurrence of any of the following events: disease progression (local, regional, or distant) during neoadjuvant therapy, disease recurrence after surgery (local, regional, or distant), contralateral breast cancer, any secondary malignancy, or death from any cause. Participants without an event at the time of last follow-up are censored.
From enrollment up to 5 years after last patient enrollment (assessed every 3 months during the first year, then every 6 months thereafter
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
大体时间：From signing of informed consent through 30 days after the last dose of study drug, or until initiation of new anticancer therapy, whichever occurs first.
Safety outcomes include: incidence of any AE, incidence of grade ≥3 AE (per NCI-CTCAE version 6.0), incidence of SAEs, incidence of AE leading to treatment discontinuation or dose modification, and incidence of AE by system organ class and preferred term. Laboratory abnormalities, vital signs, ECG parameters (QTcF, heart rate), and left ventricular ejection fraction (LVEF) are also summarized.
From signing of informed consent through 30 days after the last dose of study drug, or until initiation of new anticancer therapy, whichever occurs first.
Pathological Complete Response Rate (pCR): ypT0-is/ypN0
大体时间：At the time of surgery, performed within 4 weeks after completion of 8 cycles of neoadjuvant therapy (Cycles 1-4: 28 days/cycle; Cycles 5-8: 21 days/cycle).
pCR is defined as absence of invasive carcinoma in the breast primary tumor (ypT0/is) and absence of tumor cells in axillary lymph nodes (ypN0) on pathological examination of the surgical specimen after neoadjuvant therapy. Presence of ductal carcinoma in situ (DCIS) alone is allowed.
At the time of surgery, performed within 4 weeks after completion of 8 cycles of neoadjuvant therapy (Cycles 1-4: 28 days/cycle; Cycles 5-8: 21 days/cycle).
Ki-67 Index Change
大体时间：Baseline (pre-treatment core needle biopsy) and at surgery (post-neoadjuvant surgical specimen).
Ki-67 index is measured by immunohistochemistry (IHC) as the percentage of tumor cells with positive nuclear staining. The scale is the Ki-67 proliferation index, which ranges from 0% (minimum) to 100% (maximum). Higher scores indicate a worse outcome (higher proliferative activity). The change is calculated as Ki-67 index at surgery minus Ki-67 index at baseline. A negative value (reduction) indicates a better outcome (decreased proliferation), while a positive value (increase) indicates a worse outcome.
Baseline (pre-treatment core needle biopsy) and at surgery (post-neoadjuvant surgical specimen).

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Tang-Du Hospital

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年6月1日

初级完成 (估计的)

2028年6月1日

研究完成 (估计的)

2029年1月1日

研究注册日期

首次提交

2026年5月24日

首先提交符合 QC 标准的

2026年5月24日

首次发布 (实际的)

2026年6月1日

研究记录更新

最后更新发布 (实际的)

2026年6月11日

上次提交的符合 QC 标准的更新

2026年6月8日

最后验证

2026年6月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • TD-DASHER-01

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

IPD 计划说明

The informed consent form signed by participants does not include provisions for sharing individual participant data with external researchers.

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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