A Multicohort Study of Toripalimab in Combination With Investigator-Selected Chemotherapy for Advanced HER2-Negative Breast Cancer

Обзор

To evaluate the efficacy and safety of toripalimab in combination with investigator-selected chemotherapy in patients with recurrent or metastatic HER2-negative breast cancer who have failed prior systemic therapy.

Вмешательства

• Препарат Toripalimab
  Toripalimab
• Препарат TPC
  Treatment of Physician's Choice

Первичные конечные точки

• ORR by investigator [Срок оценки: At baseline, at the time point of every 8 weeks within first 24 weeks, thereafter every 12 weeks]

Вторичные конечные точки (5)

• PFS [Срок оценки: up to 3 years]
• DCR [Срок оценки: At baseline, at the time point of every 8 weeks within first 24 weeks, thereafter every 12 weeks]
• DoR [Срок оценки: up to 3 years]
• OS [Срок оценки: up to 3 years]
• Safety (Proportion of AEs) [Срок оценки: from time of informed consent provided to 30 days after the last dose of study therapy]

Критерии участия

Критерии включения

• Voluntary participation: the subject must give written informed consent, be compliant, and agree to attend all follow-up visits.
• Age ≥ 18 years.
• ECOG performance-status score ≤ 1 and life expectancy ≥ 3 months.
• Histologically or cytologically confirmed HER2-negative breast cancer (HER2-negative is defined as either IHC 0, IHC 1+, or IHC 2+ with a negative in-situ-hybridisation \[ISH\] result).
• For subjects with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC):

\- Must have experienced progression during/after at least one prior systemic regimen for recurrent/metastatic disease (recurrence ≤ 12 months after neoadjuvant/adjuvant therapy counts as first-line failure).

\- Cohort assignment by prior immune-checkpoint-inhibitor (ICI) exposure:

• Cohort A - ICI-pretreated:

• If ICI was given in adjuvant setting, recurrence must occur ≥ 12 months after completion of immunotherapy.
• If ICI was given in neoadjuvant or metastatic setting, best overall response must have met clinical-benefit criteria (PR, CR, or SD > 24 weeks).
• Cohort B - ICI-naïve: no prior anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, or any other antibody targeting T-cell co-stimulatory or checkpoint pathways.
• For subjects with hormone-receptor-positive (HR+) breast cancer:

• Must have progressed after ≥ 2 prior endocrine regimens in the recurrent/metastatic setting (unless investigator judges no endocrine benefit), and
• Must have progressed after ≥ 1 prior systemic chemotherapy for recurrent/metastatic disease (recurrence ≤ 12 months after adjuvant/neoadjuvant therapy counts as first-line failure).
• At least one measurable lesion per RECIST v1.1.
• Adequate organ function, defined as:

Haematology (no transfusion within 14 days):

• Haemoglobin ≥ 9 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L
• Platelet count ≥ 100 × 10⁹/L . Serum chemistry:

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• Total bilirubin ≤ 1.5 × ULN, or if total bilirubin > ULN then direct bilirubin ≤ ULN
• ALT and AST ≤ 2.5 × ULN
• Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min
• Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days before first dose and must use highly effective contraception from first dose until 6 months after last dose.

WOCBP is defined as any sexually mature female who has not undergone hysterectomy or bilateral oophorectomy and who has not experienced natural amenorrhoea for ≥ 24 consecutive months (including women with treatment-induced amenorrhoea).Men whose partners are WOCBP must also use effective contraception during the same period.

Критерии исключения

• Uncontrolled central-nervous-system metastases (symptomatic or requiring corticosteroids or mannitol for symptom control).
• Clinically significant or uncontrolled cardiac disease within 6 months before first dose, including congestive heart failure, angina, myocardial infarction, or ventricular arrhythmia.
• Malignancy within 5 years before first dose, except adequately treated basal-cell carcinoma of the skin or carcinoma in situ of the cervix.
• Active autoimmune disease requiring systemic therapy within 2 years before first dose, except vitiligo, type-1 diabetes, or residual hypothyroidism due to autoimmune thyroiditis managed with hormone replacement only.
• Uncontrolled pleural, pericardial, or ascitic fluid requiring repeated drainage.
• Documented human immunodeficiency virus (HIV) infection.
• Documented hepatitis-B infection or active hepatitis-C infection.
• Prior hypersensitivity to any component or excipient of the investigational product(s).
• Any condition judged by the investigator to render the patient unsuitable for trial participation.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Henan Cancer Hospital — Чжэнчжоу

Идентификаторы

NCT: NCT07540533 · 2025-370

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗