Molecular PD-L1 PET/CT Imaging with 89Zr-atezolizumab to Monitor Immune Responses in metastatic Triple Negative Breast Cancer: study protocol for a phase II diagnostic imaging trial.

BackgroundImmune checkpoint inhibitors (Programmed Death Ligand 1 [PD-L1] and Programmed Death 1 [PD-1] antibodies) are approved for the first line treatment of metastatic and irresectable triple negative breast cancer (mTNBC) with immunohistochemical (IHC) PD-L1 positivity on a tumor biopsy, and combined with a chemotherapy backbone. Intra- and interlesional as well as spatial heterogeneity in PD-L1 expression as well the invasive nature of tumor biopsies poses disadvantages of this method of selecting patients for the addition of PD-L1/PD-1 antibodies. Our study hypothesis is that whole body Positron Emission Tomography with computed tomography (PET/CT) imaging with a PD-L1 specific radiotracer could be a more reliable biomarker approach for the selection of patients with mTNBC who benefit from the addition from PD-L1/PD-1 antibodies. MethodsIn the phase II "Molecular PD-L1 PET/CT Imaging with 89Zr-atezolizumab to Monitor Immune Responses in metastatic Triple Negative Breast Cancer" (MIMIR-mTNBC) trial, treatment enrichment for checkpoint inhibitors is done by a baseline 89Zr-atezolizumab PET/CT followed by a tumor biopsy to determine PD-L1 by IHC. Patients with a PD-L1 positive tumor on biopsy and/or PET are treated with chemotherapy + atezolizumab. The primary aim of the study is to assess the level of statistical agreement between the reference standard (PD-L1 IHC) compared to the experimental method (PD-L1 PET) by means of Cohens kappa coefficient. The trial is registered at Clinicaltrials.org with number NCT05742269. DiscussionThe results of the MIMIR-mTNBC trial are expected to reveal the possibility of PD-L1 PET with 89Zr-atezolizumab to complement or replace the assessment of PD-L1 status by means of IHC on a tumor biopsy, and as a possible method to select patients with mTNBC that benefit from the addition of atezolizumab to a chemotherapy backbone. This non-invasive tool may provide a method that reveals relevant information about heterogeneity in the expression of the target of treatment. Trial registrationNCT05742269, Trial registered on February 23rd, 2023, at clinicaltrials.gov