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.
調査の概要
詳細な説明
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).
研究の種類
介入
入学 (推定)
20
段階
- フェーズ2
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
いいえ
説明
Inclusion Criteria:
- Age ≥18 and ≤70 years
- Histologically confirmed invasive breast cancer, HR+ (ER ≥1% and/or PR ≥1%) and HER2-low (IHC 1+ or IHC 2+/ISH-)
- No prior systemic anti-tumor therapy for breast cancer
- Stage II-III (T1cN1-2M0, T2-4N0-2M0) per AJCC 8th edition
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%
- At least one measurable lesion per RECIST 1.1
- ECOG PS 0-1
- 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
- Negative pregnancy test (for women of childbearing potential) and agreement to use adequate contraception during and for 6 months after treatment
- Willing and able to provide informed consent and comply with study procedures
Exclusion Criteria:
- Non-pathologically confirmed breast cancer
- Bilateral, inflammatory, or occult breast cancer
- Prior anticancer therapy (chemotherapy, radiotherapy, targeted therapy, endocrine therapy, etc.)
- Concurrent use of other anticancer treatments
- Other malignancy within 5 years (except cured basal cell carcinoma or cervical carcinoma in situ)
- Participation in another interventional clinical trial within 4 weeks prior to first dose
- Use of immunosuppressive agents or systemic corticosteroids (>10 mg/day prednisone or equivalent) within 2 weeks prior to first dose
- Live or attenuated vaccine within 4 weeks prior to first dose
- Major surgery unrelated to breast cancer within 4 weeks prior to first dose
- Active or history of autoimmune disease requiring systemic treatment
- Known immunodeficiency (e.g., HIV positivity) or history of organ transplantation
- 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)
- Known or suspected interstitial lung disease (ILD) or significant pre-existing pulmonary disease
- Active hepatitis B (HBsAg positive and HBV DNA ≥500 IU/mL) or hepatitis C (HCV RNA above ULN), cirrhosis, or uncontrolled severe infection
- Known bleeding or thrombotic tendency
- Allergy or contraindication to any study drug or excipient
- Pregnancy, breastfeeding, or positive pregnancy test at baseline
- Any concurrent condition that may compromise patient safety or study compliance (e.g., uncontrolled hypertension, severe diabetes, active infection)
- History of neurological or psychiatric disorders (e.g., epilepsy, dementia) or any condition deemed unsuitable by the investigator.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Dalpiciclib + Aromatase Inhibitor followed by SHR-A1811
|
CDK4/6 inhibitor, 125 mg oral tablet, taken once daily on days 1-21 of each 28 day cycle for 4 cycles.
Includes anastrozole 1 mg/day, letrozole 2.5 mg/day, or exemestane 25 mg/day, administered orally once daily for 4 cycles.
Anti-HER2 antibody-drug conjugate (ADC), 4.8 mg/kg intravenous infusion once every 3 weeks for 4 cycles
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Objective Response Rate (ORR)
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Breast-Conserving Surgery Rate
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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).
|
協力者と研究者
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スポンサー
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
2026年6月1日
一次修了 (推定)
2028年6月1日
研究の完了 (推定)
2029年1月1日
試験登録日
最初に提出
2026年5月24日
QC基準を満たした最初の提出物
2026年5月24日
最初の投稿 (実際)
2026年6月1日
学習記録の更新
投稿された最後の更新 (実際)
2026年6月11日
QC基準を満たした最後の更新が送信されました
2026年6月8日
最終確認日
2026年6月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- TD-DASHER-01
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
いいえ
IPD プランの説明
The informed consent form signed by participants does not include provisions for sharing individual participant data with external researchers.
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米国FDA規制医薬品の研究
いいえ
米国FDA規制機器製品の研究
いいえ
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