Neoadjuvant Dalpiciclib + AI → SHR-A1811 for HR+/HER2-Low Breast Cancer
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18-70
SponsorTang-Du Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Single group
Treatments tested in this trial
Dalpiciclib 125mg
DrugCDK4/6 inhibitor, 125 mg oral tablet, taken once daily on days 1-21 of each 28 day cycle for 4 cycles.
Aromatase Inhibitor
DrugIncludes anastrozole 1 mg/day, letrozole 2.5 mg/day, or exemestane 25 mg/day, administered orally once daily for 4 cycles.
SHR-A1811
DrugAnti-HER2 antibody-drug conjugate (ADC), 4.8 mg/kg intravenous infusion once every 3 weeks for 4 cycles
Treatment groups
20 Participants
are divided into 1 treatment groupGroup A: Dalpiciclib + Aromatase Inhibitor followed by SHR-A1811Experimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Objective Response Rate (ORR)
Proportion of patients achieving complete response (CR) or partial response (PR) per RECIST 1.1
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 surgerySecondary outcomes
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.
Time frame
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.
Time frame
At the time of surgery3
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.
Time frame
From enrollment up to 5 years after last patient enrollment (assessed every 3 months during the first year, then every 6 months thereafter4
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.
Time frame
Baseline (pre-treatment core needle biopsy) and at surgery (post-neoadjuvant surgical specimen).Locations
Sponsors and contacts
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Source ClinicalTrials.gov
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