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AzTrials

Breast CancerPhase 2TD-DASHER-01NCT07618923

Neoadjuvant Dalpiciclib + AI → SHR-A1811 for HR+/HER2-Low Breast Cancer

A Phase 2 study testing Dalpiciclib 125mg, Aromatase Inhibitor and SHR-A1811 in people with Breast Cancer and HR Positive/HER2 Low Breast Cancer, run by Tang-Du Hospital.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Official record
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Trial summary

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+)… Read more about this study

Who is it for?
Ages 18 to 70 years, women only
What is being tested?
Dalpiciclib 125mg, Aromatase Inhibitor and SHR-A1811
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
No sites listed yet
Study dates
Jun 2026to Jan 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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.

About this study

Official title: 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.

Read the detailed description

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).
Being tested
Dalpiciclib 125mg, Aromatase Inhibitor, SHR-A1811
Keywords
Breast Cancer, HR-positive, HER2-low, Neoadjuvant Therapy, Dalpiciclib, SHR-A1811
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dalpiciclib 125mgDrug

    CDK4/6 inhibitor, 125 mg oral tablet, taken once daily on days 1-21 of each 28 day cycle for 4 cycles.

  • Aromatase InhibitorDrug

    Includes anastrozole 1 mg/day, letrozole 2.5 mg/day, or exemestane 25 mg/day, administered orally once daily for 4 cycles.

  • SHR-A1811Drug

    Anti-HER2 antibody-drug conjugate (ADC), 4.8 mg/kg intravenous infusion once every 3 weeks for 4 cycles

Study groups in NCT07618923
Study groupRoleWhat they receive
Dalpiciclib + Aromatase Inhibitor followed by SHR-A1811ExperimentalNot described
Receives: Drug: Dalpiciclib 125mg; Drug: Aromatase Inhibitor; Drug: SHR-A1811

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR)

    Proportion of patients achieving complete response (CR) or partial response (PR) per RECIST 1.1

    Measured: 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

Secondary outcomes (5)

  1. Pathological Complete Response Rate (pCR): ypT0-is/ypN0

    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.

    Measured: 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).

  2. Breast-Conserving Surgery Rate

    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.

    Measured: At the time of surgery

  3. Event-Free Survival (EFS)

    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.

    Measured: From enrollment up to 5 years after last patient enrollment (assessed every 3 months during the first year, then every 6 months thereafter

  4. Ki-67 Index Change

    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.

    Measured: Baseline (pre-treatment core needle biopsy) and at surgery (post-neoadjuvant surgical specimen).

  5. Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

    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.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jun 2026
  2. Study startJun 2026 (estimated)
  3. Primary completionJun 2028 (estimated)
  4. Study completionJan 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07618923
Sponsor's protocol ID
TD-DASHER-01
Acronym
TD-DASHER-01
Status last verified
Jun 2026
First submitted
24 May 2026
Last updated
11 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: The informed consent form signed by participants does not include provisions for sharing individual participant data with external researchers.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dalpiciclib 125mg, Aromatase Inhibitor and SHR-A1811 in people with Breast Cancer and HR Positive/HER2 Low Breast Cancer, run by Tang-Du Hospital.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07618923.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026.

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