OPTIMUNE-LUNG : INTEGRATIVE ANALYSIS OF THE TUMOR MICROENVIRONMENT AND OPTIMIZATION OF THE IMMUNOTHERAPY DURATION IN NON-SMALL CELL LUNG CANCER PATIENTS
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
- The primary endpoint is the 12-month progression-free rate (PFR) defined as the rate of patients in confirmed and unconfirmed complete reponse (CR and Cru), confirmed and unconfirmed partial response (PR and PRu) and stable disease (SD), as per RECIST v1.1, observed at 12 months (from randomization). To be considered as confirmed (i.e. as CR or PR), claimed responses will have to be confirmed 4 weeks later. Otherwise, responses will be considered as unconfirmed (CRu, PRu).
研究概览
简要总结
The primary objective is to assess long-term benefit of PD-1 inhibition in NSCLC patients who experienced a response between 6 and 12 months after initiation of ICI (immune checkpoint inhibitor PD1/PDL-1 blockade therapy). The long-term benefit of PD1/PDL-1 inhibition will be assessed in terms of progression-free rate (PFR) at 12 months after randomization, for each therapeutic strategy (in patients discontinuing treatment and in patients continuing treatment).
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed non-small cell lung carcinoma (squamous or non squamous).
- •Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration.
- •Patient with a social security in compliance with the French law (Loi Jardé).
- •Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
- •Voluntarily signed and dated written informed consent prior to any study specific procedure.
- •Locally advanced/unresectable or metastatic disease.
- •For non-squamous histology, tumor with no oncogenic addiction: no activating EGFR mutation, no ALK or ROS1 rearrangement,
- •Treatment with ICI (immune checkpoint inhibitor PD1/PDL-1 blockade therapy): a. in first or second-line treatment as per market authorization. For patients in first line, ICI alone or ICI + chemotherapy, b. start of ICI treatment 6 to 12 months (+/- 2 weeks) before registration.
- •At least one measurable lesion according to the RECIST v1.1 criteria before ICI treatment onset and confirmed by centralized review (lesion in previously irradiated filed can be considered as measurable if progressive at inclusion according to RECIST v1.1). At least one site of disease must be uni-dimensionally ≥ 10 mm.
- •Patient with objective response (CR, PR) according to RECIST v1.1 criteria at 6 months or more and less than 12 months after ICI treatment onset. Response must be confirmed by centralized review on the basis of all CT scan carried out since the initiation of ICI treatment up to registration. PET-CT are also acceptable (several PET-CTs or CT scans compared with PET-CTs), under the following conditions: a. Target lesions must be evaluable on PET-CT according to RECIST v1.
- •This will be determined by the centralized radiologist at the time of the review. If target lesions are not evaluable according to RECIST v1.1, patient will not be eligible. b. PET-CT is acceptable only for the centralized review. If not available, an additional CT scan must be performed within four weeks prior to registration (+1 week tolerance) to be used as baseline tumor assessment. Patient must be then followed using the same technique throughout the duration of the protocol.
- •At least one lesion that can be biopsied for research purpose. Note that in case of complete response or too small size lesion, the investigator must ensure the availability of suitable paraffin embedded (FFPE) archived tumor material (primary or metastatic site).
- •Performance status < 2.
排除标准
- •Female who is pregnant or breast-feeding.
- •Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study.
- •Hypersensitivity to one of the active substances or to one of the excipients
- •Any contraindication to pursue ICI treatment as per investigator judgement.
- •Previous enrolment in the present study.
- •Individual deprived of liberty or placed under legal guardianship.
结局指标
主要结局
The primary endpoint is the 12-month progression-free rate (PFR) defined as the rate of patients in confirmed and unconfirmed complete reponse (CR and Cru), confirmed and unconfirmed partial response (PR and PRu) and stable disease (SD), as per RECIST v1.1, observed at 12 months (from randomization). To be considered as confirmed (i.e. as CR or PR), claimed responses will have to be confirmed 4 weeks later. Otherwise, responses will be considered as unconfirmed (CRu, PRu).
The primary endpoint is the 12-month progression-free rate (PFR) defined as the rate of patients in confirmed and unconfirmed complete reponse (CR and Cru), confirmed and unconfirmed partial response (PR and PRu) and stable disease (SD), as per RECIST v1.1, observed at 12 months (from randomization). To be considered as confirmed (i.e. as CR or PR), claimed responses will have to be confirmed 4 weeks later. Otherwise, responses will be considered as unconfirmed (CRu, PRu).
The 12-month PFR will be assessed, independently for each therapeutic strategy.
The 12-month PFR will be assessed, independently for each therapeutic strategy.
Imaging will be centrally reviewed for all patients by an expert radiologist. Reviewed data will be used for the primary endpoint analysis.
Imaging will be centrally reviewed for all patients by an expert radiologist. Reviewed data will be used for the primary endpoint analysis.
次要结局
- Secondary endpoints will be assessed, independently for each therapeutic strategy:
- The rate of patients who develop progression (as per RECIST v1.1) due to secondary resistance after obtaining a response to PD1/PDL-1 inhibition (secondary progression) will be assessed, independently for each therapeutic strategy, at 12 months from randomization, based on radiological centralized review.
- Duration of response (DoR) defined as the time interval between the first response (complete or partial response as per RECIST v1.1) to the time of the first documentation of disease progression.
- Progression-free survival (PFS) defined as the time interval between the date of randomization and the date of progression or death, whichever occurs first. Progression will be determined according to RECIST v1.1.
- Overall Survival (OS) defined as the time interval between the date of randomization and the date of death (of any cause).
- Toxicity profile of each therapeutic strategy will be assessed during the study. Events will be graded according to the Common Terminology Criteria of Adverse Events (CTCAE) v5 from the NCI. AEs and SAEs will be coded according to MedDRA.
- Number of patients retreated by ICI will be described in Arm B. Similarly, for arm A-patients, number of patients treated by subsequent systemic therapy will be described.
- Biomarker study: integrated analysis of blood samples and tumor biopsies performed at randomization and progression to reveal markers of response and resistance.
研究者
Pr Antoine ITALIANO
Scientific
Institut Bergonie