Abstract
TPS759 Background: Immune checkpoint inhibitors (ICIs) have changed the treatment landscape for renal cell carcinoma (RCC). Despite this, responses to single-agent anti-PD-1 occur in only 25% of patients. Biomarkers such as PD-L1 expression and tumor infiltrating lymphocyte density may predict response, but require invasive biopsies that fail to fully interrogate the complex tumor microenvironment throughout the patient. Efforts are underway to identify who will benefit from ICIs. Among these are the use of radiolabeled antibodies against PD-L1. We propose to combine the specificity of anti-PD-L1 antibodies with the sensitivity, resolution, and quantification offered by positron emission tomography to develop immunoPET (iPET). iPET will allow real-time monitoring of tumor and its microenvironment in-vivo, and may correlate with response and toxicity with ICIs. Methods: The anti-PD-L1 antibody Atezolizumab is conjugated to Zirconium-89 via desferrioxamine (DFO). 89Zr-DFO-Atezolizumab will be administered to two cohorts of approximately 20 patients. Cohort 1 have localized RCC prior to undergoing surgery, and cohort 2 have metastatic RCC prior to treatment with an ICI. The main exclusion criteria are existing use of an ICI or comorbidities that would preclude treatment with an ICI. All subjects will receive an IV injection of 89Zr-DFO-Atezolizumab followed 7 days (+/- 1 day) by a PET/CT scan. Subjects in cohort 2 will receive treatment with ICI per clinician discretion. Subjects will receive a repeat scan if disease recurrence is documented (cohort 1) or should progression or toxicity occur after treatment with an ICI (cohort 2). Biopsy of disease recurrence (cohort 1) will be standard, and encouraged for sites of disease progression on ICI (cohort 2). Co-primary endpoints are an exploratory analysis of 89Zr-DFO-Atezolizumab uptake on PET/CT with PD-L1 expression assessed by IHC in patients undergoing surgery (cohort 1) and to evaluate uptake across metastatic sites and explore the relationship with response or toxicity with ICI therapy (cohort 2). An investigational new drug approval has been granted for 89Zr-DFO-Atezolizumab (IND 143266) and accrual commenced 1 October 2019. Clinical trial information: NCT04006522.
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