Reverse HER2-negative Immune Resistant Breast Cancer
Ориентир для пациента и семьи
Простыми словами
Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.
- Что изучают
- В протоколе указаны: Retinoic Acid, anti-PD-1 antibody and chemotherapy.
- Кому может быть актуально
- Состояния в реестре: HER2 Negative Breast Cancer. Базовые параметры: 18 лет — 70 лет · Женщины.
- Что важно проверить
- Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
- Где проводится
- Китай
- Следующий шаг
- Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →
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Обзор
This is a Phase II, open-label study evaluating the efficacy and safety of combined treatment (retinoic acid) with immune checkpoint inhibitor in HER2-negative breast cancer patients who progressed during previous immune checkpoint inhibitors.
Подробное описание
This is a Phase II, open-label study evaluating the efficacy and safety of combined treatment (retinoic acid) with immune checkpoint inhibitors in metastatic HER2-negative breast cancer patients who progressed during or following previous immune checkpoint inhibitors. HER2-negative breast cancers include luminal breast cancers and triple-negative breast cancers.
Current clinical studies on immunotherapy for luminal breast cancer are limited, with inconsistent results across trials. The KEYNOTE-028 study reported an objective response rate (ORR) of only 12% for pembrolizumab in PD-L1-positive, previously treated advanced luminal breast cancer patients, demonstrating limited efficacy. The GIADA phase II trial revealed a pathological complete response (pCR) rate of 16.3% with neoadjuvant chemotherapy followed by immunotherapy in luminal breast cancer. Additionally, trials such as NCT02779751 and NCT03051659 also indicated limited clinical benefits from immunotherapy. However, the I-SPY2 platform showed that combinations like olaparib, paclitaxel, and immunotherapy or wP-AC chemotherapy with immunotherapy could improve pCR rates in high-risk patients. Despite advancements, immunotherapy benefits are limited in luminal breast cancer compared to other cancers, with advanced-stage patients more likely to develop resistance.
Recent clinical studies on advanced triple-negative breast cancer have shown that immunotherapy combined with chemotherapy demonstrates superior clinical efficacy compared to traditional chemotherapy alone. Phase III trials such as IMPassion130 and Keynote-522 have confirmed that PD-1/PD-L1 inhibitors used with chemotherapy significantly improve progression-free survival, overall survival, and pathological complete response rates. However, compared to other malignancies, triple-negative breast cancer patients still show relatively low overall response rates to immunotherapy: treatment-naïve patients achieve objective response rates of only 10-20% with immunotherapy monotherapy, though this improves to 56% when combined with chemotherapy, extending median progression-free survival to 7.2 months. Unfortunately, efficacy decreases significantly in later treatment lines, with objective response rates falling to just 10.6-15.9% after multiple previous treatments. Thus, strategies to overcome immunotherapy resistance or increase the sensitivity of immunotherapy efficacy are urgently needed for HER2-negative breast cancer patients.
The preclinical results of our center show that retinoic acid can enhance the anti-tumor immune response by promoting the peroxidation of macrophages, increasing the infiltration and function of cytotoxic CD8+ T cells, inhibiting the growth of tumors in mice. Based on the preclinical study, the investigators designed this study to enroll metastatic HER2-negative breast cancer patients who have progressed during or following immunotherapy, and to explore the efficacy of retinoic acid combined with immunotherapy at a clinical level, providing new strategies of combined treatment for HER2-negative breast cancer patients.
Вмешательства
- Препарат Retinoic Acid
Retinoic acid 20mg tid, p.o. - Препарат anti-PD-1 antibody and chemotherapy
PD-1 antibody SHR1210 200mg q2w chemotherapy (whether and which should be given depends on the treatment regimen before enrollment)
Первичные конечные точки
- Objective Response Rate (ORR) [Срок оценки: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months]
- Clinical Benefit Rate (CBR) [Срок оценки: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months]
- Immune changes in peripheral blood [Срок оценки: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months]
Вторичные конечные точки (4)
- Disease Control Rate (DCR) [Срок оценки: Baseline through end of study, assessed up to 6 months]
- Progression Free Survival (PFS) [Срок оценки: Randomization to death from any cause, through the end of study, assessed up to 6 months]
- Safety and treatment-related AEs [Срок оценки: Randomization to death from any cause, through the end of study, assessed up to 12 months]
- Biomarker analysis [Срок оценки: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months]
Критерии участия
Критерии включения
- ECOG Performance Status of 0, 1, or 2
- Metastatic or locally advanced, histologically confirmed luminal breast cancer (defined as: ER positive when immunohistochemistry shows >1% positive tumor cells, PR positive when >1% tumor cells are positive, and HER2 negative when scored as 0-1+ or when HER2 2+ shows no amplification by FISH or CISH) or triple negative breast cancer (defined as: ER negative when immunohistochemistry shows <1% positive tumor cells, PR negative when <1% tumor cells are positive, and HER2 negative when scored as 0-1+ or when HER2 2+ shows no amplification by FISH or CISH).
- Radiologic/objective evidence of recurrence or disease progression after immunotherapy (combined with targeted therapy or chemo ) for metastatic breast cancer (MBC)
- Adequate hematologic and end-organ function, laboratory test results, obtained within 14 days prior to initiation of study treatment.
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined for each specific treatment arm
- Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1)
- have the cognitive ability to understand the protocol and be willing to participate and to be followed up.
Критерии исключения
- Symptomatic, untreated, or actively progressing CNS metastases
- Active or history of autoimmune disease or immune deficiency
- Significant cardiovascular disease
- History of malignancy other than breast cancer within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death
- Treatment with chemotherapy, radiotherapy, immunotherapy or surgery (outpatient clinic surgery excluded) within 3 weeks prior to initiation of study treatment.
- Pregnancy or breastfeeding, or intention of becoming pregnant during the study
- History of allergies to the drug components of this trial
- History of eosinophilosis or mastocytosis
- Patients who have been using oral steroid hormones for a long time will need to stop for 4 weeks if they have used them occasionally in the past
Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.
Здоровые добровольцы: Нет
Дизайн исследования
- Распределение
- Не применимо
- Модель
- Одна группа
- Маскирование
- Открытое
- Основная цель
- Лечение
Центры проведения
Китай · 1 центр
- Fudan University Shanghai Cancer Center — Шанхай
Идентификаторы
NCT: NCT06731140 · 2411307-7