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

NCT07618923 | Not Yet Recruiting Phase 2

• 1 other identifier: TD-DASHER-01
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief 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+), 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.

Conditions

Breast Cancer; HR Positive/HER2 Low Breast Cancer

Keywords

Breast Cancer; HR-positive; HER2-low; Neoadjuvant Therapy; Dalpiciclib; SHR-A1811

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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

Secondary Outcomes (5)

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

  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).

• Breast-Conserving Surgery Rate

  At the time of surgery

• Event-Free Survival (EFS)

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

• Ki-67 Index Change

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

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  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.

Study Arms (1)

Dalpiciclib + Aromatase Inhibitor followed by SHR-A1811

EXPERIMENTAL

Drug: Dalpiciclib 125mg; Drug: Aromatase Inhibitor; Drug: SHR-A1811

Interventions

Dalpiciclib 125mg DRUG

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

Dalpiciclib + Aromatase Inhibitor followed by SHR-A1811

Aromatase Inhibitor DRUG

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

Dalpiciclib + Aromatase Inhibitor followed by SHR-A1811

SHR-A1811 DRUG

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

Dalpiciclib + Aromatase Inhibitor followed by SHR-A1811

Eligibility Criteria

• Age: 18 Years - 70 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tang-Du Hospital: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

dalpiciclib; Aromatase Inhibitors

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2026
• First Posted: June 1, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: June 11, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share