⁸⁹Zr-DFO-durvalumab PET/CT prior to durvalumab treatment in patients with recurrent or metastatic head and neck cancer

Background: In the PINCH study we performed ⁸⁹Zr-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-DFO-durvalumab PET-imaging and predict disease control rate during durvalumab treatment. Secondary aims were to correlate ⁸⁹Zr-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 PET-imaging 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 bloodpool. 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 1.4 (95%CI 0.5-3.9, P = 0.54) and (HR 1.3 (95%CI 0.5-3.6, P = 0.61) 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]Zr-DFO-durvalumab-uptake did not correlate to PD-L1 CPS score, but did correlate to [¹⁸F]FDG SUV peak (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.