460 Spatial distribution of infiltrating T lymphocytes with Immunoscore® CR T cells exhaustion test helps stratification of NSCLC patients treated with PD1/PDL1 inhibitors in the PIONeeR project

Background PD1/L1 Immune Checkpoint Inhibitors (ICI) have significantly improved long-term outcome in about 20% of advanced Non Small Cells Lung Cancer (NSCLC) patients (pts), but 80% present primary or secondary resistance. The PIONeeR project (NCT03493581) aims to predict the response/resistance to PD1/L1 ICIs in advanced NSCLC pts through a comprehensive agnostic multiparametric and longitudinal biomarkers assessment. Data presented here are a focus on the quantification of tumor infiltration by lymphocytes, their activation as potential markers of the resistance to treatment by ICI. Methods Advanced NSCLC pts with available archived tumor tissue at screening visit (VS), treated with standard PD1/L1 ICIs (nivolumab, pembrolizumab or atezolizumab), alone (2nd line or more) or combined with chemotherapy (1st line), were re-biopsied at 6 weeks (V2) of treatment. PD1/L1 ICIs overall response rate (ORR) was assessed by RECIST 1.1 every 6 weeks. The multiplex IHC test ”Immunoscore® CR T Cells Exhaustion” (IS TCE) quantifies cytotoxic lymphocytes expressing three checkpoints: PD1, LAG3, TIM3, extrapolating their exhaustion status, both in the stroma and parenchyma. The unsupervised neural-network-based machine learning algorithm SOM (Self-Organizing Maps) was used to classify samples based on the 27 IS TCE variables. Statistical significance of survival differences between groups was evaluated using the log-rank test. Results Among the first 100 pts, (male (64%), smokers (91,8%), Conclusions IS TCE test may help stratifying and predicting responders to anti PD1/L1 therapy through checkpoint expressing lymphocytes quantification and spatial distribution. Additional tests performed on the PIONeeR cohort to explore other aspects of the immune response to cancer should complete these results. Acknowledgements This work is supported by French National Research Agency (ANR-17-RHUS-0007), a partnership of AMU, APHM, AstraZeneca, Centre Leon Berard, CNRS, HalioDx, ImCheck Therapeutics, Innate Pharma, Inserm, Institut Paoli Calmettes and sponsored by AP HM. Drug supply is funded by AstraZeneca. Special thanks to patients and families. Trial Registration NCT03493581 Ethics Approval The study is conducted in accordance with Good Clinical Practice and the French applicable regulatory requirements (Public Health Code, article L.1121-1/La loi n° 2012–300 du 5 mars 2012 relative aux recherches impliquant la personne humaine (dite loi Jarde), the applicable subject privacy requirements, and the ethical principles that are outlined in the Declaration of Helsinski. The study was approved by the French Ethic Committee, CPP Ouest II - Angers, ref. CPP: 2028/08, Ref ANSM (French competent authority) 2018020500208, 2018072600120, 2019083000148. Freely given written informed consent was signed and obtained from each individual participating in the study, before any study specific procedure was undertaken and after the provision of information about the study by the investigator during a physician-patient consultation and sufficient time for reflection.