Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (PIONeeR-BioMarkers (BM) Profiling)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 450
- 试验地点
- 2
- 主要终点
- Immuno-monitoring
研究概览
简要总结
PIONeeR study is a prospective, multicenter study without administration of an investigational product.
The promotion and funding will be done by the Assistance Publique Hôpitaux de Marseille (APHM), the coordination by AMU. There will be 3 principal investigational clinical centres in France:
- Service d'Oncologie Multidisciplinaire et Innovations Thérapeutiques in APHM, Marseille, supervised by Prof. L. Greillier
- Medical Oncology Department of Centre Léon Bérard, Lyon, supervised by Prof. M. Pérol
- Unité d'Oncologie Thoracique, CHU Larrey /Oncopôle, Toulouse, supervised by Prof. J. Mazières.
Some secondary centres, nearby the three principal mentioned above, will be associated to ensure recruitment of patients, in accordance to provisional planning.
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The primary objective is to validate the existence and distribution of the hypothetical immune profile (within blood and tumoral tissue) explaining primary or adaptive resistance to standard PD-1 inhibitors monotherapy, in NSCLC patients.
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The secondary objectives are to better characterize :
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PK/PD relationships,
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inter-patient PK variability,
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If systemic exposure levels could be predictive of efficacy of PD-1 ICI, in NSCLC patients.
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Some exploratory objectives are :
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to assess a predictive value of a panel of endothelial biomarkers, in NSCLC patients.
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to compare predictive immune & endothelial biomarker profiles with those of sensitive tumors.
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to better understand which profiles track significantly with progression following PD-1 ICI administration, in order to improve advanced NSCLC patients' stratification, for future clinical trials.
详细描述
Visits will match with usual schedule of patient's appointments with their referent oncologist or for injections of ICIs, when blood sampling or biopsies will be done. Feces will be collected by patients themselves, at home (optional).
The same day of registration for either an EMA approved first line PD-1 or PD-L1 inhibitor in combination with platinum-based chemotherapy OR a standard 2nd or 3rd line PD-(L) 1 ICIs monotherapy (to date, Nivolumab, Pembrolizumab, Atezolizumab), 450 advanced NSCLC patients will undergo a screening visit (Vs). If they are eligible, after signing an informed written consent, they will be blood-sampled specifically for the study:
- after 3 or 4 weeks (V1-1st assessment of PK/PD, after the 2d course),
- after 6 weeks (V2),
- after 8 or 9 weeks (V3-2nd assessment of PK/PD, after the last course),
- after 12 weeks of treatment (V4- samples for 3rd assessment of PK/PD and other analyses ).
- after 18 weeks (V5- samples for 4th assessment of PK/PD and other analyses,),
- after 24 weeks of treatment (V6-5th assessment of PK/PD and other analyses).
Patients will also be re-biopsied (primitive tumor or metastasis) specifically for the study, at V2. Referent patients'oncologist will opt for the simplest technical approach with a minimal risk exposure for patients. Standard procedures will be implemented for subsequent patient's monitoring.
Patients will also provide remaining samples from pre-treatment surgical resections/biopsies (primitive tumor or metastasis).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •- Patients must be over 18 years
- •Patients must have histologically confirmed diagnosis of advanced (proven stade IV) or recurrent NSCLC,
- •Their ECOG Performance Status must be of 0 or 1
- •EITHER patients must be previously untreated and eligible for an EMA approved first line PD-1 or PD-L1 inhibitor in combination with platinum-based chemotherapy, irrespective of their tumor histology
- •These EMA approved first line combinations must be reimbursed by French Health Insurance or at least, must have an Authorization for Temporary Use (ATU) in France
- •OR Patients must display disease progression after at least one line of platinum-based chemotherapy and eligible for a registered second or third line PD-1 or PD-L1 inhibitor in monotherapy (to date, Nivolumab, Pembrolizumab, Atezolizumab)
- •For patients registered for a 2nd or 3rd line, those with known actionable molecular alteration (EGFR activating mutation, ALK rearrangement, ROS1 rearrangement) should have received a specific inhibitor
- •Patients must have an available archived tissue from a standard tumor biopsy for PD-L1 assessment, done before PD-1 ICI initiation
- •Patients must have an available archived tissue from a standard tumor biopsy for PD-L1 assessment, done before PD-1 ICI initiation
- •Patients must have adequate organ functions
- •Patients must have provided a signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
排除标准
- •Patients previously untreated and eligible for a first line PD-1 or PD-L1 inhibitor in monotherapy
- •Combination of PD-1 or PD-L1 inhibitor with bevacizumab
- •Exclusive bone progression
- •Exclusive cerebral progression not amenable to surgical biopsy
- •Absence of a target lesion according to RECIST criteria 1.1
- •Life expectancy of less than 3 months
- •Severe adverse events from PD-1 treatment
- •Abnormal coagulation contraindicating biopsy
- •History of hemorrhagic or thrombotic stroke, TIA or other CNS bleeds
- •Active uncontrolled or serious infection (viral, bacterial or fungal)
- •Active infection including VHB and VHC infections
- •Individuals deprived of liberty or placed under the authority of a tutor
- •Patient unable to understand, read and/or sign an informed consent
- •Any condition which in the Investigator's opinion would jeopardize compliance with the protocol of the study
- •Patients without Health insurance scheme or Universal Medical Coverage (CMU) or any equivalent scheme
- •Pregnant or breast-feeding women
结局指标
主要结局
Immuno-monitoring
时间窗: 54 MONTHS
BLOOD SAMPLES to characterize B, T, NK, and dendritic cell subsets and monocyte populations as well as Innate Lymphoid Cells (ILC) with cytometry analysis
次要结局
- measure the Circulating endothelial cells (CECs)(54 MONTHS)
- Minimum Plasma Concentration Cmin of anti PD (L) 1 treatment(54 MONTHS)
- Maximum Plasma Concentration Cmax of anti PD (L) 1 treatment(54 MONTHS)
- lymphocytes DNA extraction's(54 MONTHS)
- Measure the number of somatic mutations(54 MONTHS)