113 [89Zr]Zr-DFO-avelumab PET/CT in early stage NSCLC patients INTRODUCTION In de last decade, immune checkpoint inhibitors (ICI) targeting programmed cell death protein-1/ programmed cell death ligand-1 (PD-1/PD-L1) have changed the therapeutic landscape of patients with lung cancer1,2. Currently, pembrolizumab (anti-PD-1) and durvalumab (anti-PD-L1) are registered as first-line treatment for stage IV NSCLC and consolidation treatment in stage III disease, respectively3,4. First results of neo-adjuvant PD-(L)1 antibodies with or without chemotherapy in patients with stage Ib - IIIb NSCLC also favor the use of ICI in earlier treatment phases5-7. Responses to ICI are predominantly observed in patients with high tumor PD-L13,4. The subsequent registration of ICI-treatment for patients with PD-L1 positive tumors, highlights the clinical implications of tumor PD-L1 expression and warrants its accurate assessment. However, the heterogenous and dynamic nature of PD-L1 expression in tumor lesions impairs the accuracy of immunohistochemical PD-L1 assessment on a tumor biopsy8. To improve treatment efficacy of ICI, better understanding of the role of PD-L1 expression in anticancer immune responses is critical. Molecular PET-imaging can visualize whole-body distribution of PD-L1 using radiolabeled anti-PD-L1 antibodies 9,10. This technique allows to study aspects of the mechanism of action of ICI that are complementary to blood- or tissue-based assays. Previously, PD-L1 PET-imaging has been performed using 89Zr-labeled antibodies targeting PD-L1 in patients with advanced stages of various cancers11-13. The primary aim of the current study is to assess the safety and feasibility of [89Zr]Zr-DFO-avelumab PD-L1 PET-imaging and correlate this to PD-L1 expression in tumor lesions in NSCLC patients. Secondary aims include the safety and tolerability of neo-adjuvant avelumab in patients with resectable early-stage NSCLC, as well as the correlation of [89Zr]Zr-DFO-avelumab to pathological response to avelumab. 6
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