Encouraging clinical data emerging in the field of tumor immunotherapy have demonstrated that therapies focused on enhancing T cell responses against cancer can result in a significant survival benefit in patients with Stage IV cancer. PD-L1 is an extracellular protein that downregulates immune responses primarily in peripheral tissues through binding to its two receptors PD-1 and B7-1. Interruption of the PD L1/PD-1 pathway by the PD-L1 targeting antibody MPDL3280A, represents an attractive strategy to reinvigorate tumor-specific T cell immunity. For PD1/PD-L1 pathway inhibition PD-L1 tumor surface expression was proposed as a potential biomarker. In early clinical trials, PD-L1 expression has been associated with response to PD1/PD-L1 inhibition. However, other clinical trials reported response to PD1/PD-L1 checkpoint inhibitors in a big patient groups who were PD-L1-negative assessed by a single biopsy. Another obstacle to using PD-L1 expression as predictive biomarker might be its potential heterogeneous expression and fast dynamics PD-L1 tumor expression and whole body distribution, as well as baseline activation status of the immune system are being assessed in three investigational imaging trials MPDL3280A-img-042015, 89Zr-CD8 imaging or IL2-img--UMCG-2015.~To be able to evaluate the investigational imaging - 89Zr-MPDL3280A-PET, 89Zr-CD8 imaging and 18F-FB-IL2-PET - as complementary tools for selection of patients to be treated with MPDL3280A, within this treatment trial we will assess safety, tolerability and anti-tumor activity of MPDL3280A in cancer patients, who have undergone investigational imaging. Acquired data could lead to improved, more patient friendly, more easily accessible and possibly less expensive procedures for patient selection. Subsequently, the efficacy of (combinations of) checkpoint inhibition could also be improved, thus preventing unnecessary toxicity and reducing health care costs.
To be able to evaluate the investigational imaging - 89Zr-MPDL3280A-PET, 89Zr-CD8 imaging and 18F-FB-IL2-PET - as complementary tools for selection of patients to be treated with MPDL3280A, within this treatment trial the investigators will assess safety, tolerability and anti-tumor activity of MPDL3280A in cancer patients, who have undergone investigational imaging.