2024 World Conference on Lung Cancer (WCLC) - Posters-P1.09C.03 IMMUNOResist: Defining the Immunophenotype of Immunotherapy Resistance with PD-L1 and CD8 Novel Tracer PET

P1.09C.03 IMMUNOResist: Defining the Immunophenotype of Immunotherapy Resistance with PD-L1 and CD8 Novel Tracer PET

Pdf Summary

IMMUNOResist is a pilot study aiming to investigate mechanisms behind immunotherapy resistance in non-small cell lung cancer (NSCLC). Conducted at the Peter MacCallum Cancer Centre in Melbourne, the study focuses on analyzing PD-L1 expression and CD8 T-cell infiltration in patients undergoing radiotherapy post-progression on earlier immunotherapy treatments. Using two novel PET tracers, 89Zr-durvalumab and 89Zr-crefmirlimab berdoxam, researchers aim to understand changes in PD-L1 expression and the immune microenvironment during treatment.<br /><br />The study primarily targets NSCLC patients with an ECOG performance score of 0-1, irrespective of PD-L1 status or genetic mutations. Imaging assessments will be performed with CD8 PET/CT before and after radiotherapy, and with 89Zr-durva PET/CT post-radiotherapy. Comparisons will be made using FDG PET/CT as a reference to evaluate tracer efficacy.<br /><br />Endpoints include both qualitative and quantitative imaging evaluations—measuring metrics like SUVmax, SUVmean, SUVpeak, and the percentage injected dose (%ID)—to compare CD8 and 89Zr-durva PET/CT scans against FDG PET/CT. Additionally, these PET/CT findings will be cross-referenced with tissue-based PD-L1 immunohistochemistry and analyses of peripheral blood mononuclear cells (PBMCs), TCR, and cytokines to provide a comprehensive view of the host immune response.<br /><br />The study includes translational biopsies, with liquid biopsies performed before and after radiotherapy. This project has received funding from the Victorian Cancer Agency and involves collaborations with AstraZeneca Pty. Ltd and ImaginAB Pty. Ltd, who provide the tracers used for imaging.<br /><br />By examining these facets, IMMUNOResist seeks to delineate the immunophenotype of therapy-resistant NSCLC, offering insights into personalized approaches for managing radiotherapy in immune checkpoint inhibitor-resistant cancers.

Asset Subtitle

Fiona Hegi-Johnson

Meta Tag

Speaker Fiona Hegi-Johnson

Topic Metastatic NSCLC – Local Therapies

Keywords

IMMUNOResist

immunotherapy resistance

non-small cell lung cancer

PD-L1 expression

CD8 T-cell infiltration

PET tracers

radiotherapy

imaging assessments

translational biopsies

personalized approaches