The Efficacy and Safety of Trastuzumab Rezetecan (SHR-A1811) in HER2-Low Unresectable/Metastatic Breast Cancer Patients With Visceral Crisis

Официальное название

Trastuzumab Rezetecan (SHR-A1811) Versus Chemotherapy of Physician's Choice in Patients With HER2-Low Unresectable/Metastatic Breast Cancer Complicated With Visceral Crisis：A Randomized, Prospective, Open-Label Phase II Trial.

Обзор

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.

Вмешательства

• Препарат Trastuzumab Rezetecan
  Trastuzumab Rezetecan 4.8mg/kg, IV, Day 1, Q3W
• Препарат Chemotherapy of Physician's Choice
  Chemotherapy of Physician's Choice, including nab-paclitaxel, Eribulin, Capecitabine, Vinorelbine, Gemcitabine.

Первичные конечные точки

• Progression-Free Survival (PFS) [Срок оценки: From the start of treatment to 36 month]

Вторичные конечные точки (4)

• Clinical Benefit Response (CBR) [Срок оценки: From the start of treatment to 36 month]
• Objective Overall Response Rate (ORR) [Срок оценки: From the start of treatment to 36 month]
• Overall Survival (OS) [Срок оценки: From the start of treatment to 36 month]
• Adverse events (AEs) [Срок оценки: From the start of treatment to 36 month]

Критерии участия

Критерии включения

• Age: ≥18 years old and ≤75 years old;
• Pathologically confirmed HER2-Low unresectable or metastatic breast cancer;
• Visceral crisis is defined as severe organ dysfunction as assessed by signs, symptoms and laboratory studies, resulting from rapid progression of neoplastic disease and indicative of substantial visceral compromise that may serve as an indication for more aggressive therapeutic intervention, including：a）Liver visceral crisis: rapidly increasing bilirubin >1.5 × ULN in the absence of Gilbert's syndrome or biliary tract obstruction；b）Lung visceral crisis: rapidly increasing dyspnoea at rest, not alleviated by drainage of pleural effusion；c）Other visceral crises: the evaluation is conducted by the clinician based on the definition of visceral crisis specified in the ABC7 guideline.
• 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) ≥ 80 ×10\^9/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.

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Cancer Hospital, Chinese Academy of Medical Sciences — Пекин

Идентификаторы

NCT: NCT07203729 · MA-BC-II-117

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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