Immunotherapy is widely administrated as anticancer treatment in metastatic setting. Despite a proved efficacy in several cancer types and clinical situations, it exists a wide variability of responses in terms of efficacy and toxicity. The rate of responders depends mostly on the type of pathology, with 40% of responders among melanoma patients, 20-30% among lung and head and neck cancer patients and only 1% of responders among pancreatic cancer patients. Thus, the main challenge today is to be able to select patients for whom the treatment is likely to be effective. Several studies suggested that tumors with a high mutational burden and expressing PD-L1 are better responders to immunotherapy. However, a proportion of PD-L1 negative cancers responds to immunotherapy, suggesting that other parameters have to be considered together with PD-L1 expression. Of that, the immunotherapy clearance seems to have an impact on overall survival, but larger studies, including different molecules and cancer types, are needed to better understand the correlation between the clearance and the response to immunotherapy. Tumor cells released from the primary tumor in the blood circulation (CTCs, for circulating tumor cells) are considered as "liquid biopsies", as they contain the entire genetic and phenotypic information representative of the tumor, including PD-L1 expression. Thus, the variation of PD-L1 expression under treatment can be easily followed-up on blood samples collected during the time. The objective of MADMAS is to study the correlation between the immunotherapy clearance, measured at the different times during treatment, and the variation of the number of CTCs expressing PD-L1 after two cures of treatment. MADMAS will enroll patients with lung or head and neck cancers, treated with an immunotherapy-based therapy. Blood samples will be collected at the baseline and before the first two cures of treatment. The immunotherapy clearance will be measured with an innovative approach of Mass Spectrometry, and PD-L1 expression will be measured on CTCs, purified with a highly sensitive microfluidics technology.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
75
Blood draws will be realized at the following time points: C1T1: at the baseline, before treatment administration. C1T2: cycle 1, after treatment administration. C2T1: the day of the 2nd cycle, before treatment administration. C2T2: the day of 2nd cycle, after treatment administration. C3T1: the day of the 3rd cycle, before treatment administration. C3T2: the day of 3rd cycle, after treatment administration.
Croix Rousse Hospital
Lyon, France
Lyon Sud Hospital
Pierre-Bénite, France
Immunotherapy clearance (mL/min) and number of PD-L1 (absolute number) positive CTCs after two cycles of treatment (composite criteria)
The clearance and the number of PD-L1 positive cells will be measured on blood samples collected the day of the third immunotherapy administration (each cycle is 14 to 28 days, depending on the type of immunotherapy).
Time frame: At the end of cycle 2 (each cycle is 21 days)
Overall survival
time elapsed between the first immunotherapy administration and the death
Time frame: 2 years
Progression free survival
time elapsed between the first immunotherapy administration and progression
Time frame: 2 years
level of PD-L1 expression on primary tumor tissue
The level of PD-L1 expression will be measured by ICH on tissue from primary tumor surgery/biopsy through study completion, an average of 2 years.
Time frame: 2 years
Baseline transcriptomic profile of CTCs isolated form peripheral blood
Baseline transcriptomic profile of CTCs isolated form peripheral blood: the transcriptomic profile of CTCs will be analyzed by NGS (Next-Generation Sequencing) from blood samples collected at cycle 1 day 1, before treatment administration.
Time frame: Day 1 of cycle 1, before treatment administration (cycle length: 14 days for nivolumab treatment and 21 days for pembrolizumab treatment)
1st cycle transcriptomic profile of CTCs isolated form peripheral blood
The transcriptomic profile of CTCs will be analyzed by NGS (Next-Generation Sequencing) from blood samples collected after the 1st cycle of treatment (cycle length between 14 and 21 days depending on the type of immunotherapy)
Time frame: Day 1 of cycle 2, before treatment administration (cycle length: 14 days for nivolumab treatment and 21 days for pembrolizumab treatment)
2nd cycle transcriptomic profile of CTCs isolated form peripheral blood
The transcriptomic profile of CTCs will be analyzed by NGS (Next-Generation Sequencing) from blood samples collected at the end of cycle 2 (each cycle is 21 days).
Time frame: Day 1 of cycle 3, before treatment administration (cycle length: 14 days for nivolumab treatment and 21 days for pembrolizumab treatment)
identification of CTCs transcriptomic signatures, associated to immunotherapy efficacy or toxicity
the CTCs transcriptomic profile (measure 4) will be obtained with the NGS method; the analyses of these profiles will imply statistical models of logistic regression (Lasso Method). These data will be compared with clinical data on efficacy (PFS measured at 2 years after the beginning of treatment) and toxicity (stopping treatment for toxicity before the third cycle).
Time frame: 2 years
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