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

Tang-Du Hospital

Status and phase: Not yet enrolling; Phase 2

Conditions: Breast Cancer; HR Positive/HER2 Low Breast Cancer

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

Study type: Interventional

Funder types: Other

Identifiers

NCT07618923

TD-DASHER-01

Details and patient eligibility

About

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.

Full description

Not necessary.

Enrollment: 20 estimated patients

Sex: Female

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

Dalpiciclib + Aromatase Inhibitor followed by SHR-A1811

Experimental group

Treatment:

Drug: Aromatase Inhibitor

Drug: SHR-A1811

Drug: Dalpiciclib 125mg