The Efficacy and Safety of Trastuzumab Rezetecan (SHR-A1811) in HER2-Low Unresectable/Metastatic Breast Cancer Patients With Visceral Crisis
- Conditions
- HER2-Low Unresectable/Metastatic Breast Cancer Complicated With Visceral Crisis
- Interventions
- Drug: Chemotherapy of Physician's Choice
- Registration Number
- NCT07203729
- Brief Summary
The goal of this clinical trial is to learn if Trastuzumab Rezetecan (SHR-A1811) is safe and tolerable for patients with HER2-Low unresectable/metastatic breast cancer complicated with visceral crisis. Participants will take Trastuzumab Rezetecan every three weeks, until disease progression or intolerable toxicity.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Female
- Target Recruitment
- 184
- Age: ≥18 years old and ≤75 years old;
- Pathologically confirmed HER2-Low unresectable or metastatic breast cancer;
- Investigators assess that the patient is at risk of rapid disease progression and presents signs, clinical symptoms, or laboratory abnormalities of visceral metastasis, including：a）Hepatic crisis: Rapid elevation of bilirubin > 1.5 × upper limit of normal (ULN) in the absence of Gilbert syndrome or biliary obstruction；b）Pulmonary crisis: Rapid exacerbation of dyspnea at rest, which is not relieved by pleural effusion drainage；c）Other visceral crises: Symptomatic visceral metastasis.
- Patients whom investigators deem to have indications for single-agent chemotherapy.
- Sufficient bone marrow function, defined as follows：a) Neutrophil count (ANC) ≥ 1,500/mm³ (1.5 × 10⁹/L)；b) Platelet count (PLT) ≥ 100,000/mm³ (100 × 10⁹/L)；c) Hemoglobin (Hb) ≥ 80 g/L；
- Patients who have received ≤ 1 line of chemotherapy in the advanced stage are permitted.
- Patients who have received endocrine therapy in the advanced stage are permitted.
- Previous treatment with CDK4/6 inhibitors is permitted.
- Previous or concurrent local treatment for symptom relief is permitted.
- For female subjects who are premenopausal or not surgically sterilized:
A serum pregnancy test must be performed within 7 days before the first dose of study drug, with a negative result. They must agree to either abstain from sexual activity or use a medically approved highly effective contraceptive method from the time of signing the informed consent form, throughout the study period, and for 1 year after the last dose of study drug.
- Patients must voluntarily participate in this study, sign the informed consent form, have good compliance, and be willing to cooperate with follow-up.
- Have received treatment with new antibody-drug conjugates (ADCs) at any stage of breast cancer.
- Are deemed by the investigator as unsuitable for systemic chemotherapy.
- Have had other malignant tumors within the past 5 years, excluding cured carcinoma in situ of the cervix, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma (patients with other malignant tumors that occurred more than 5 years before randomization and were cured solely by surgery are eligible for enrollment).
- Have undergone major surgical procedures or suffered significant trauma within 4 weeks prior to randomization, or are expected to undergo major surgical treatment.
- Have severe heart disease or cardiac discomfort, including but not limited to the following conditions：a) A history of heart failure or systolic dysfunction (left ventricular ejection fraction [LVEF] < 50%)；b) High-risk angina pectoris requiring treatment or cardiac arrhythmias；c) Clinically significant valvular heart disease；d) ECG findings indicating transmural myocardial infarction；e) Poorly controlled hypertension.
- Have a known history of allergy to any component of the drugs in this protocol.
- Have a history of immunodeficiency, including HIV infection, or other acquired or congenital immunodeficiency diseases.
- Have a known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
- Have a known history of psychotropic substance abuse or drug addiction.
- Are pregnant or lactating women, or women of childbearing age who are unwilling to use effective contraceptive measures throughout the trial period and within 7 months after the last administration of the study drug.
- Have severe diseases, other comorbidities that would interfere with the planned treatment, or any other conditions that make them unsuitable for participation in this study (e.g., active hepatitis B, pulmonary infection requiring treatment).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1：Trastuzumab Rezetecan Trastuzumab Rezetecan - Arm 2：Chemotherapy of Physician's Choice Chemotherapy of Physician's Choice -
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) From the start of treatment to 36 month Progression-Free Survival is defined as the time from randomization to first documented disease progression (PD) using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) or death from any cause, whichever occurred first. The PFS will be will be estimated using Kaplan-Meier method. A Kaplan-Meier curve, median PFS, hazard ratio with appropriate confidence intervals will be reported.
- Secondary Outcome Measures
Name Time Method Clinical Benefit Response (CBR) From the start of treatment to 36 month CBR is percentage of participants with best (confirmed) PR or CR or SD for at least 6 months. PR or CR or SD is according to RECIST version 1.1. The CBR will be reported by percentage with each arms and appropriate confidence intervals.
Objective Overall Response Rate (ORR) From the start of treatment to 36 month ORR is defined as percentage of participants with best (confirmed) overall response (BOR) of either CR or PR. ORR was assessed by the investigator according to RECIST version 1.1 and is based on BOR, which is defined as best response recorded from start of study treatment until disease progression/recurrence or death. The ORR will be reported by percentage with each arms and appropriate confidence intervals.
Overall Survival (OS) From the start of treatment to 36 month Overall Survival , defined as the time from the start of treatment to the date of death, regardless of the cause of death. The OS will be estimated using Kaplan-Meier method. A Kaplan-Meier curve, median OS, hazard ratio with appropriate confidence intervals will be reported.
Adverse events (AEs) From the start of treatment to 36 month AEs were graded according to the National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. The type, grade and frequency of AEs will be reported.