Prediction of ICIs efficacy in combination with chemotherapy remains an unmet need in patients (pts) with advanced NSCLC. The PIONeeR trial aims to predict response/resistance to PD1/L1 ICIs through a comprehensive multiparametric BMs analysis.
We focused on the first 155 ECOG PS0-1 pts treated with pembrolizumab in combination with platinum-based chemotherapy as 1st line therapy. Tumor tissue was collected at baseline and pts were re-biopsied at 6 weeks, and blood-sampled every cycle throughout 24 weeks. Immune contexture was characterized in tumor & blood through FACS for circulating immune cell subtypes quantification and endothelial activation, blood soluble factors dosage, dual- & multiplex IHC / digital pathology to quantify immune cells infiltrating the tumor, WES for TMB & ICI plasma pharmacokinetics, leading to 298 assessed BMs. Multimodal data integration through supervised machine learning (SML) was performed with bootstrap LASSO on a train (N=116) and a test dataset (N=39) to establish a BMs signature able to predict progression-free-survival (PFS) at 1 year.
Pts were mainly male (65%), smokers (96%) and <70yrs (82%). Tumors were mainly nonsquamous (87%) with PD-L1 TPS>1% in 38.4% of cases. With a median follow of 11.4 months, median PFS was 9.8 months and median overall survival was not reached. Using baseline data, SML identified a 15 BMs signature including classical (age, ECOG PS, PD-L1 TPS…) but also experimental parameters (CD45+ CD16+ cells density in tumor, CD45- CD73+ cells density in stroma, tissue factor and CD31+ CD41+ AnC+ microparticles blood concentrations…) with high predictive performance for PFS. On the train dataset, C-index was 0.79±0.13 and AUC was 0.81±0.28. These scores were confirmed on the test dataset, with C-index of 0.80 and AUC of 0.84.
The PIONeeR trial provides a novel comprehensive BMs analysis to establish predictive models of response/resistance to ICI in advanced NSCLC pts. Combination of BMs can individually predict outcomes of chemo-immunotherapy.
Clinical trial identification
Legal entity responsible for the study
Assistance Publique des Hôpitaux de Marseille.
French National Research Agency.
F. Monville, L. Ghezali, J. Fieschi-Meric: Financial Interests, Personal, Full or part-time Employment: Veracyte. All other authors have declared no conflicts of interest.