2266P - IMMUcan consortium: Focus on the first results of the non-small cell lung cancer (NSCLC) cohort

Background

Immune checkpoint blockers have changed the treatment landscape for patients with NSCLC, however, response is often limited. PD-L1 protein expression is the only validated biomarker to enrich in responders and understanding resistance mechanisms to propose rationally driven combination therapies is clearly needed. To this end, IMMUcan, a pan-European consortium, is aiming at gaining a better understanding of the tumor microenvironment (TME) by combining broad molecular profiles of the tumor with spatially resolved cellular information of the TME and clinical information for 3,000 patients, with NSCLC a core indication of this project.

Methods

The first NSCLC cohort is composed of 191 patients from the EORTC SPECTAlung (NCT02214134) program, and 48 patients prospectively recruited in SPECTA (NCT02834884). All patients were diagnosed with NSCLC (any histology, any stage), FFPE material was collected at time of diagnosis, prior to treatment. Whole exome sequencing (WES), total RNA sequencing (RNAseq), multiplex immunofluorescence (mIF) and imaging mass cytometry (IMC) data was collected for each patient and analysed.

Results

The cohort contains a majority of adenocarcinoma (153 adenocarcinoma, 55 squamous carcinoma, 31 other) and early stage disease patients (74 stage I, 57 stage II, 63 stage III and 44 stage IV, 1 unknown). Median age at registration was 67, 100 patients were female and 139 male, and the majority were current or former smoker (163 patients). Stage is the strongest clinical predictor or survival (64.1 months for stage 1, 60.8 for stage 2, 58.3 for stage 3 and 14.1 for stage 4). 15% of adenocarcinoma patients had a driver mutation (EGFR, BRAF) and stage and histology are the main drivers of heterogeneity for RNAseq. T cell infiltration was assessed on all FFPE samples and is associated with improved overall survival. Tertiary lymphoid structures were identified in the majority of samples (∼70%), with various number of B cells and differing expression of lymphocyte maturation markers.

Conclusions

Further integration of the cellular and molecular data are ongoing and additional biomarkers will be presented at the conference.

Clinical trial identification

SPECTA NCT02834884.

Editorial acknowledgement

Legal entity responsible for the study

European Organisation for Research and Treatment of Cancer.

Funding

IMI2 JU grant agreement 821558, supported by EU’s Horizon 2020 and EFPIA.

Disclosure

M. Morfouace, H.S. Hong: Financial Interests, Personal, Other, Employee: Merck Healthcare. T. Cufer: Financial Interests, Personal, Invited Speaker: MSD, Pfizer, Roche; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Takeda; Financial Interests, Institutional, Local PI: MSD. K. Oselin: Financial Interests, Personal, Advisory Board: MSD, Takeda, AstraZeneca, Janssen, Amgen, Roche; Financial Interests, Institutional, Research Grant: Takeda, Roche, Pfizer. J. Oliveira: Financial Interests, Personal, Other, Advisory board, Invited Speaker: AstraZeneca, Roche, Novartis, Janssen; Financial Interests, Personal, Invited Speaker: GSK, BMS, MSD, Bayer; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Institutional, Funding, Investigator Initiated Clinical Trial funding: AstraZeneca. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, OSE immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, Eisai, Genzyme Corporation, Inivata, Ipsen, Turning Point Therapeutics. All other authors have declared no conflicts of interest.