83 [89Zr]Zr-DFO-durvalumab PET/CT before durvalumab treatment in R/M SCCHN patients INTRODUCTION Squamous cell carcinoma of the head and neck (SCCHN) is the seventh most common cancer worldwide, with up to 900,000 new diagnoses in 2020 1. Patients with recurrent/metastatic (R/M) SCCHN with no curative options have a poor prognosis 2. However, a subset of patients derives durable responses from immune checkpoint inhibitors (ICI) targeting Programmed cell death 1 (PD-1) or its ligand (PD-L1) 3-5, although selecting those patients upfront remains challenging. Patients who benefit most from ICI often express high levels of tumor PD-L1 as analyzed by immunohistochemistry, using different assays, scoring protocols and cut-offs 5-8. Since June 2019, pembrolizumab received FDA and EMA-approval as 1st line treatment of R/M SCCHN patients with an immunohistochemistry combined positive score (CPS) of at least ≥1. Thus, pre-treatment assessment of PD-L1 has major clinical implication, although there are also patients with a PD-L1 negative tumor biopsy who benefit from ICI 9-11. Therefore, there is a clinical need to better understand ICI responses and the caveats that remain with selection based on PD-L1 expression in tumor biopsies. The role and expression of PD-L1 in anti-cancer immune responses is complex and warrants a biomarker that enables monitoring its heterogenous and dynamic expression in different (tumor) tissues 12. Molecular imaging with radiolabeled tracers targeting PD-1/PD-L1 allows non-invasive visualization of all accessible PD-1/ PD-L1 13,14. This approach overcomes important limitations of immunohistochemistry analyses, including invasive biopsies and sampling errors 15,16. It is a complementary tool to blood and tissue sampling, potentially providing relevant information for patient selection and to steer drug development 17. The first clinical PD-1/PD-L1 imaging studies were performed with 89Zr-labeled atezolizumab (anti-PD-L1) and nivolumab (anti-PD-1) in patients with metastatic breast cancer, bladder cancer and non-small cell lung cancer (NSCLC), demonstrating a correlation between tracer-uptake and treatment response 18,19. So far, no PD-L1 PET imaging studies have been performed in patients with R/M SCCHN. The primary aim of the PD-L1 ImagiNg to prediCt durvalumab treatment response in SCCHN (PINCH) study was to assess the safety and feasibility of [89Zr]Zr-DFO-durvalumab PD-L1 PET imaging and to predict durvalumab disease control rate in patients with R/M SCCHN. Secondary aims were to investigate the correlation of [89Zr]Zr-DFO-durvalumab uptake to 1) PD-L1 expression measured on tumor biopsies, 2) [18F]FDG uptake and 3) treatment response of individual tumor lesions. 5
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