355O - Artificial intelligence-powered spatial analysis of tumor microenvironment (TME) in nasopharyngeal carcinoma (NPC) patients treated with immune checkpoint inhibitors (ICI)

Background

ICI have promising activity in phase II trials of patients (pts) with recurrent or metastatic NPC. We investigated whether AI-powered spatial tumor infiltrating lymphocyte analysis (AI-STIL) of NPC TME cell subpopulations correlate with clinical outcome in pts treated with ICI-based therapy.

Methods

A total of 73 NPC pts treated with Nivolumab+Gemcitabine (Niv+Gem; KCSG HN17-11), Niv+Ipilimumab (Niv+Ipi, NCT03097939), Niv alone (Niv, NCT02339558), or Avelumab+Axitinib (Ave+Axi, NCT04562441) who have matched H&E slides before treatment were included in this exploratory post-hoc analysis. Lunit SCOPE IO (Lunit, Korea) was applied to spatially analyze TIL, macrophages (MP), fibroblasts (FB), and endothelial cells (EC) in the intratumoral area and adjacent stroma. Cell populations were analyzed.

Results

In all merged dataset, the median progression-free survival (mPFS) and overall survival (mOS) were 7.3 mo and 30 mo, respectively. ORR/mPFS by each regimen were 38.7%/13.8 m in Niv+Gem (n=31), 36.4%/5.4 m in Niv+Ipi (n=22), 36.4%/3.7 m in Niv (n=11), and 0%/5.4 m in Ave+Axi (n=9), respectively. In TIL subgroup analysis, mPFS was significantly higher in high intratumoral TIL (iTIL) than low iTIL group (hazard ratio, HR 0.44, p=0.0081), but no difference in stromal TIL (sTIL, HR 1.14, p=0.6681). mPFS was longer in the high intratumoral MP subgroup (HR 0.5, p=0.0209), but not the stromal MP subgroup (HR 0.9, p=0.7278). In FB and EC analyses, mOS was lower in high stromal FB (sFB) than low sFB (HR 2.44, p=0.0148), but there were no significant differences in survival outcomes across the other cell subgroups.

Conclusions

Interactive TME analysis powered by AI suggested that intratumoral TIL or macrophage, not stromal residues, are clinically significant in the NPC patients treated with ICI.

Drs. Bhumsuk Keam and Darren Wan-Teck Lim equally contributed to the study.

Clinical trial identification

KCT0003189, NCT03097939, NCT02339558, NCT04562441.

Editorial acknowledgement

Legal entity responsible for the study

Lunit.

Funding

Lunit.

Disclosure

B. Keam: Financial Interests, Personal, Invited Speaker: Merck, Lily; Financial Interests, Personal, Advisory Board: Handok, TrialInformatics, ImmunOncia, NeoImmunetech, Beigen; Financial Interests, Personal, Coordinating PI: MSD Oncology, AstraZeneca, Ono Pharmaceutical. D.W. Lim: Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board: MSD, Roche, BeiGene; Financial Interests, Institutional, Trial Chair, Grant funding for investigator-sponsored study: Bristol Myers Squibb; Financial Interests, Institutional, Steering Committee Member: Novartis. C. Ock: Financial Interests, Personal and Institutional, Officer: Lunit. T. Lee, C. Oum: Financial Interests, Personal and Institutional, Officer: Lunit. B. Goh: Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board: Bayer Healthcare; Financial Interests, Personal, Other, Consultancy: Adagene pharmaceutical; Financial Interests, Institutional, Research Grant, Support for investigator initiated trial: MSD; Financial Interests, Institutional, Other, Pharmaceutical support for clinical trial: BMS; Financial Interests, Institutional, Other, Pharmaceutical support for investigator initiated clinical trial: Taiho pharmaceuticals; Financial Interests, Institutional, Coordinating PI: Adagene, Bayer; Financial Interests, Institutional, Local PI: Pfizer; Financial Interests, Institutional, Local PI, Conducting clinical trial: alx; Financial Interests, Institutional, Local PI, Pharmaceutical phase 1 trial: Novartis; Non-Financial Interests, Institutional, Other, Lead clinical trial platform of the Singapore Translational Cancer Consortium: Consortium for Clinical Research and Innovation Singapore; Non-Financial Interests, Personal, Member: ASCO. A.T.C. Chan: Financial Interests, Personal, Advisory Board: MSD, Tessa Therapeutics Ltd; Financial Interests, Personal, Other, Consultancy: MSD; Financial Interests, Personal, Other, Biomarker testing for MK-3475 KN122 program: MSD; Financial Interests, Personal, Writing Engagement: Springer; Financial Interests, Personal, Other, Travel and accommodation expenses to attend conference: Roche; Financial Interests, Institutional, Research Grant, Neoadjuvant Pembrolizumab-Gemcitabine-Cisplatin Followed by Concurrent Pembrolizumab-Chemoradiation and Maintenance Pembrolizumab for Stage IVA Nasopharyngeal Cancer: Merck Sharp & Dohme (Asia) Ltd; Financial Interests, Institutional, Research Grant, Biomarker study for NEO-SPACE MISP-56746: MSD International GmbH; Financial Interests, Institutional, Research Grant, AXEL - Axitinib-Avelumab Combination in Recurrent or Metastatic Nasopharyngeal Cancer - A Multicenter Phase 2 Trial: Pfizer Corporation Hong Kong Limited; Financial Interests, Institutional, Research Grant, Clinical Development of a Urine Test for Screening Urinary Tract Cancers: Angene Biotechnology Limited; Financial Interests, Institutional, Research Grant, NRG Oncology #HN007 An Open-label, Phase II Study of Platinum-Gemcitabine With or Without Nivolumab in the First Line of Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma: NRG OncologyFoundation, Inc.; Non-Financial Interests, Personal, Advisory Role: Immunomic Therapeutics, Inc, Angene Biotechnology Limited, Owlstone Medical Limited. B.B.Y. Ma: Financial Interests, Personal, Invited Speaker, Advisory Board/Consultancy: Novartis, BMS, MSD; Financial Interests, Personal, Advisory Board, Consultancy: Y-biologics, Boehringer Ingelheim, Merck Serono; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board, Ad board and consultancy: Viracta Therapeutics; Financial Interests, Personal, Other, Consultancy: Alentis; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Merck Serono; Financial Interests, Institutional, Research Grant, Research Grant Preclinical: Novartis; Non-Financial Interests, Personal, Principal Investigator, NRG oncology study PI: NRG oncology. All other authors have declared no conflicts of interest.