PD-L1 Positron Emission Tomography Imaging in Patients With Non-Small Cell Lung Cancer: Preliminary Results of the ImmunoPET Phase 0 Study

Abstract

ImmunoPET is a multicenter, single arm, phase 0-1 study of 89Zr-DFO-Sq-durvalumab (89Zr-durvalumab), a novel PET tracer, designed to interrogate the expression of PD-L1 in patients with NSCLC. Clinically relevant findings from phase 0 are presented here. Phase 0 was designed to investigate tracer biodistribution and safety in patients with metastatic NSCLC with PD-L1 expression >25%. After 60MBq/70kg 89Zr-durvalumab infusion, PET/CT images were acquired at days 0, 1, 3 or 5 ± 24h. Baseline FDG PET/CT was performed prior to PD-L1 PET imaging. All five patients recruited to phase 0 completed the full imaging protocol. The only reported adverse event was a transient asymptomatic increase in respiratory rate. At the time of PD-L1 imaging, two patients were in complete remission on FDG-PET after treatment with osimertinib and pembrolizumab; neither showed PD-L1 tracer uptake in previous tumor sites. All three patients with active tumor had received radiotherapy to some or all disease sites prior to PD-L1 imaging. With the exception of a single disease site, specific uptake of 89Zr-durvalumab uptake was seen in tumours, with increasing uptake in tumor seen up to Day 5 post-injection. Patient 1, who had multiple metastases, including brain and bone, showed more intense 89Zr-durvalumab uptake in recently irradiated bone lesions than un-irradiated lesions and uptake was also observed in treated brain metastases.. One patient, who experienced rapid growth of a single lung lesion that had acquired resistance to pembrolizumab, showed no significant 89Zr-durvalumab in that lesion, despite recent radiotherapy. In patient 5, 89Zr-durvalumab uptake was observed in the viable rim of a large, recently irradiated adrenal oligometastasis. 89Zr- durvalumab imaging was safe and detected known viable tumor at multiple sites. Recently irradiated tumours showed the highest uptake and in another, a single site of immunotherapy resistant disease showed minimal tracer uptake. PD-L1 imaging may have utility in patients with NSCLC treated with radiotherapy.