Reverse Triple Negative Immune Resistant Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
This is a Phase II, open-label, seven-arm parallel study evaluating the efficacy and safety of combined treatment (sodium cromoglicate, choline, efavirenz, SHR 1811, SHR 2102, mecapegfilgrastim, theophylline) with immune checkpoint inhibitor or immune checkpoint inhibitor rechallenge(AK131) in mTNBC (triple negative breast cancer) patients who progressed during previous immune checkpoint inhibitors.
详细描述
This is a Phase II, open-label, three-arm parallel study evaluating the efficacy and safety of combined treatment (sodium cromoglicate, choline, efavirenz, SHR 1811, SHR 2102, mecapegfilgrastim) with immune checkpoint inhibitor or immune checkpoint inhibitor rechallenge(AK131) in mTNBC (triple negative breast cancer) patients who progressed during or following previous immune checkpoint inhibitors. The investigators have achieved a breakthrough in the FUTURE study with an ORR (objective response rate) reaching 52.6% in IM (immunomodulatory) subtype TNBC patients. Despite this, there are still some IM subtype patients resistant to immunotherapy. How to reverse immunotherapy resistance or how to increase the sensitivity of immunotherapy efficacy, has become an urgent clinical problem to be solved. The preclinical results of our center show that sodium cromoglicate, choline, efavirenz, SHR 1811, SHR 2102, mecapegfilgrastim, AK131, theophylline play a potentially important role in regulating the tumor immune microenvironment and can inhibit the growth of tumors in mice, and enhance the efficacy of PD-1 inhibitors in mice. Based on preclinical studies, the investigators designed this study to enroll mTNBC patients who have progressed during or following immunotherapy, and to explore the efficacy of these drugs at a clinical level, providing new strategies of combined treatment for TNBC patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •ECOG Performance Status of 0, 1, or 2
- •Metastatic or locally advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)
- •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.
排除标准
- •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
- •For the Mecapegfilgrastim group, patients had previously received PEG-rhG-CSF in combination with immunotherapy.
研究组 & 干预措施
HER2 0
HER2 0 expression
干预措施: SHR-A2102 (Drug)
HER2 0
HER2 0 expression
干预措施: SHR-1316 (Drug)
AK131
AK131(CD73/PD1 bispecific antibody)
干预措施: AK131 (Drug)
Efavirenz
Efavirenz with anti-PD-1 immunotherapy
干预措施: Efavirenz (Drug)
HER2 low
HER2 low expression
干预措施: SHR-A1811 (Drug)
HER2 low
HER2 low expression
干预措施: SHR-1316 (Drug)
Choline
Choline with anti-PD-1 immunotherapy
干预措施: Choline (Drug)
Choline
Choline with anti-PD-1 immunotherapy
干预措施: anti-PD-1 antibody and chemotherapy (Drug)
Sodium cromoglicate
Sodium cromoglicate with anti-PD-1 immunotherapy
干预措施: anti-PD-1 antibody and chemotherapy (Drug)
Sodium cromoglicate
Sodium cromoglicate with anti-PD-1 immunotherapy
干预措施: Sodium Cromoglicate (Drug)
Efavirenz
Efavirenz with anti-PD-1 immunotherapy
干预措施: anti-PD-1 antibody and chemotherapy (Drug)
Mecapegfilgrastim
Mecapegfilgrastim with anti-PD-1 immunotherapy
干预措施: anti-PD-1 antibody and chemotherapy (Drug)
Mecapegfilgrastim
Mecapegfilgrastim with anti-PD-1 immunotherapy
干预措施: Mecapegfilgrastim (Drug)
Theophylline
Theophylline with anti-PD-1 immunotherapy
干预措施: Theophylline (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Immune changes in peripheral blood
时间窗: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
次要结局
- Disease Control Rate (DCR)(Baseline through end of study, assessed up to 6 months)
- Progression Free Survival (PFS)(Randomization to death from any cause, through the end of study,assessed up to 6 months)
- Safety and treatment-related AEs(Randomization to death from any cause, through the end of study,assessed up to 12 months)
- Biomarker analysis2(Baseline until disease progression or loss of clinical benefit, assessed up to 6 months)
- Biomarker analysis3(Baseline until disease progression or loss of clinical benefit, assessed up to 6 months)
- Biomarker analysis1(Baseline until disease progression or loss of clinical benefit, assessed up to 6 months)