Background Immune 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.

Methods In 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 Cohen’s kappa coefficient. The trial is registered at Clinicaltrials.org with number NCT05742269.

Discussion The 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 registration NCT05742269, Trial registered on February 23rd, 2023, at clinicaltrials.gov

The authors have declared no competing interest.

NCT05742269

This study is funded by a grant from the Swedish Cancer Society (Dnr 19 0189 Us) to Professor Jonas Bergh, Radiumhemmets Research Fund 2020 to Renske Altena, Swedish Breast cancer Society 2020 to Renske Altena and Percy Falk Foundation to Professor Rimma Axelsson. Atezolizumab, SP142 IHC antibodies and Foundation One CDx is kindly provided by Roche AB. The funders did not and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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