Efficacy and Safety of Trastuzumab Rezetecan Followed by CDK4/6 Inhibitors and Endocrine Therapy in HR+/HER2-Low/Ultra-Low Advanced Breast Cancer
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Trastuzumab rezetecan + CDK4/6 inhibitors + endocrine therapy.
- Who it may be relevant to
- Registry conditions: Advanced Breast Cancer. Basic parameters: from 18 years · Female.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- China
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
This multicenter, prospective phase II clinical trial evaluates the efficacy and safety of sequential Trastuzumab rezetecan followed by dalpiciclib plus endocrine therapy (fulvestrant or aromatase inhibitors) in 45 patients with HR+/HER2-low/ultra-low advanced breast cancer. Enrolled patients will receive Trastuzumab rezetecan monotherapy for 6-8 cycles until clinical benefit, then transition to CDK4/6 inhibitors with endocrine therapy until disease progression or unacceptable toxicity. The primary endpoint is progression-free survival (PFS), with secondary endpoints including objective response rate (ORR), overall survival (OS), and treatment-related adverse events (TRAEs). The study will be conducted at Sun Yat-sen Memorial Hospital and collaborating centers.
Interventions
- Drug Trastuzumab rezetecan + CDK4/6 inhibitors + endocrine therapy
sequential Trastuzumab rezetecan followed by CDK4/6 inhibitors (Dalpiciclib, Abemaciclib, Ribociclib, Palbociclib) plus endocrine therapy (fulvestrant or aromatase inhibitors)
Primary outcome measures
- Progression-free survival (PFS) [Time frame: 2-year PFS]
Secondary outcome measures (6)
- Objective Response Rate (ORR) [Time frame: ORR (CR+PR rate per RECIST 1.1) with ≥30% tumor reduction at 2 years post-enrollment, assessed by investigators]
- Clinical Benefit Rate (CBR) [Time frame: CBR (CR+PR+SD≥24 weeks rate per RECIST 1.1) at 2 years post-enrollment, assessed by investigators.]
- Disease Control Rate (DCR) [Time frame: DCR (CR+PR+SD rate per RECIST 1.1) at 2 years post-enrollment (investigator-assessed)]
- Overall Survival (OS) [Time frame: OS (time from enrollment to death) at 2-year follow-up (primary endpoint)]
- Treatment-Related Adverse Events (TRAEs) [Time frame: TRAEs (all AEs from first dose to 30 days post-treatment) graded by CTCAE v5.0, with causality assessment]
- Quality of Life (QoL) [Time frame: QoL (EORTC QLQ-C30) evaluated serially from baseline to treatment discontinuation over 2 years]
Eligibility criteria
Inclusion criteria
Participants must meet all of the following criteria:
1\. Female patients aged ≥18 years. 2. Pathologically confirmed HER2-low/ultra-low, HR-positive unresectable or metastatic breast cancer:
- HER2-low: IHC 1+ or IHC 2+/ISH-negative；HER2-ultra-low: IHC 0 with membranous staining (>0 but <1+). HR+: ≥10% tumor cells with ER/PR nuclear staining (verified by central pathology review).
- Disease stage: Recurrent/metastatic disease; locally recurrent cases must be deemed unresectable by investigators.
3\. Prior therapy:
- Disease progression after endocrine therapy (ET) + CDK4/6 inhibitor in the advanced/metastatic setting.
- Progression within 12 months of adjuvant ET + CDK4/6 inhibitor allowed.
- ≤1 line of prior ET and ≤1 line of chemotherapy for advanced disease. 4. Measurable disease per RECIST 1.1 (including lytic/mixed bone-only metastases).
5\. ECOG PS 0-1. 6. Adequate organ function (no transfusions/G-CSF within 2 weeks prior):
- Hematologic: ANC >1.5×10⁹/L; platelets >90×10⁹/L; Hb >90 g/L.
- Hepatic: Total bilirubin ≤ULN (≤2×ULN if Gilbert's syndrome). ALT/AST ≤1.5×ULN (≤5×ULN with liver metastases). Alkaline phosphatase ≤2.5×ULN.
- Renal: BUN/Cr ≤1.5×ULN.
- Cardiac: LVEF ≥50%;
- QTcF <470 ms. 7. Voluntary participation with signed informed consent.
Exclusion criteria
Participants will be excluded if they meet any of the following conditions:
- Prior anti-HER2 therapy at any stage (including HER2-ADCs such as T-DM1 or T-DXd).
- Significant cardiac disease, including:
1\) Heart failure or systolic dysfunction (LVEF <50%). 2) High-risk/treated angina or arrhythmias (e.g., Type II Mobitz II/third-degree AV block, ventricular tachycardia).
3\) Clinically significant valvular disease. 4) ECG-confirmed transmural myocardial infarction. 5) Uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg). 3. Interstitial lung disease (ILD)/pneumonitis:
- History of non-infectious ILD requiring steroids.
- Current ILD or suspected ILD that cannot be ruled out by imaging at screening. 4. Impaired drug absorption due to:
1\) Dysphagia, chronic diarrhea, intestinal obstruction, or other factors affecting oral medication intake.
5\. Uncontrolled third-space effusions (e.g., pleural/peritoneal effusions) not manageable by drainage.
6\. Pregnancy, lactation, or unwillingness to use effective contraception during and for 7 months post-treatment.
7\. Other exclusions:
- Severe comorbidities interfering with treatment (e.g., active HBV, pulmonary infections requiring therapy).
- Any condition deemed unsuitable by investigators.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
China · 1 center
- Sun Yat-sen Memorial Hospital — Guangzhou
Identifiers
NCT: NCT07037199 · SDE-BRCA