Sarah Verhoeff

82 Chapter 5 ABSTRACT Background In this PD-L1 ImagiNg to predict durvalumab treatment response in SCCHN (PINCH) study we performed [89Zr]Zr-DFO-durvalumab (anti-PD-L1) PET/CT in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) prior to monotherapy durvalumab treatment. The primary aims were to assess safety and feasibility of [89Zr]Zr-DFOdurvalumab PET-imaging and predict disease control rate during durvalumab treatment. Secondary aims were to correlate [89Zr]Zr-DFO-durvalumab uptake to tumor PD-L1 expression, [18F]FDG uptake, and treatment response of individual lesions. Methods In this prospective multicenter phase I-II study (NCT03829007), patients with incurable R/M SCCHN underwent baseline [18F]FDG PET and CT or MRI imaging. Subsequently, PD-L1 PETimaging was performed 5 days after 37MBq [89Zr]Zr-DFO-durvalumab administration. To optimize imaging conditions, dose-finding was performed in the first 14 patients. For all patients, durvalumab treatment (1500mg/4 weeks, IV) was started <1 week after PD-L1 PET imaging and continued until disease progression or unacceptable toxicity (maximum 24 months). CT evaluation was assessed according to RECIST 1.1 every 8 weeks. PD-L1-expression was determined by combined positive score (CPS) on (archival) tumor-tissue. [89Zr]Zr-DFO-durvalumab uptake was measured in [18F]FDG -positive lesions, primary and secondary lymphoid organs, and blood pool. Results In total, 33 patients with locoregional recurrent (n=12) or metastatic SCCHN (n=21) were enrolled. [89Zr]Zr-DFO-durvalumab injection was safe. A dose of 10mg durvalumab resulted in highest tumor-to-blood-ratios. After a median follow-up of 12.6 months, overall response rate was 26%. The disease control rate at 16 weeks was 48% with a mean duration of 7.8 months (range 1.7-21.1). On a patient level, [89Zr]Zr-DFO-durvalumab SUVpeak or tumor-to-blood ratio could not predict treatment response (HR 1.5 (95%CI 0.5-3.9, p=0.45) and (HR 1.3 (95%CI 0.53.3, p=0.60) respectively). Also, on a lesion level, [89Zr]Zr-DFO-durvalumab SUVpeak showed no substantial correlation to treatment response (Spearman ρ 0.45, p= 0.051). Lesional [89Zr]ZrDFO-durvalumab-uptake did not correlate to PD-L1 CPS score but did correlate to [18F]FDG SUVpeak (Spearman ρ 0.391, p= 0.005). Conclusion PINCH is the first PD-L1 PET/CT study in patients with R/M SCCHN and has shown the feasibility and safety of [89Zr]Zr-DFO-durvalumab PET/CT in a multi-center trial. [89Zr]Zr-DFO-durvalumab -uptake did not correlate to durvalumab treatment response.