By performing a 89Zr-MPDL3280A-PET scan prior to treatment with MPDL3280A, the uptake of the tracer in the primary and metastatic tumor lesions and normal organ distribution can be evaluated, as well as the use of a 89Zr-MPDL3280A-PET as a complementary tool for patient selection in the future.
Non Small Cell Lung Cancer
Other: 89Zr-MPDL-3280A-PET scans
|Study Design:||Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||ImmunoPET Imaging With 89Zr-MPDL3280A in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer, Bladder Cancer or Triple-negative Breast Cancer Prior to MPDL3280A Treatment|
- Description of 89Zr-MPDL3280A PK by measuring standardized uptake value (SUV) on the 89Zr-MPDL3280A-PET scans [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Tumor and immune cell PD-L1 expression analysis in a fresh pre-treatment biopsy, and if available archival tumor biopsy, will be correlated to 89Zr-MPDL3280A tumor uptake, evaluated by measuring standardized uptake value (SUV) on the 89Zr-MPDL3280A-PET. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Safety assessment through summaries of adverse events, changes in laboratory test results, changes in vital signs, and exposure to 89Zr-MPDL3280A. Adverse event data will be recorded and summarized according to NCI CTCAE v4.0. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||July 2015|
|Estimated Study Completion Date:||July 2017|
|Estimated Primary Completion Date:||July 2017 (Final data collection date for primary outcome measure)|
Other: 89Zr-MPDL-3280A-PET scans
89Zr-MPDL3280A tracer injection and 89Zr-MPDL-3280A-PET scans
The Programmed cell death protein 1 (PD1)/Programmed death-ligand 1 (PD-L1) axis is an important immune checkpoint for T cell activation that is used by tumors to evade the host immune response. Blocking signaling with the PD-L1 antibody MPDL3280A results in ongoing T cell activity and can induce durable tumor regression across numerous solid tumor types. PD-L1 is not only expressed by tumor cells but also by immune cells, activated vascular endothelial cells and in immune privileged sites such as the eye. An obstacle to using PD-L1 expression as predictive biomarker might be its potential heterogeneous expression and fast dynamics. For PD1/PD-L1 pathway inhibition PD-L1 tumor surface expression, positive in 40-100% of all melanoma patients and 35-95% of all non-small-cell lung cancer (NSCLC) patients, 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 up to 47% of PD-L1-negative melanomas assessed by a single biopsy. In bladder cancer weak to strong PD-L1 expression has been reported in 30% of the patients, however also response in PD-L1-negative patients has been seen. For triple-negative breast cancer (TNBC) little is known, but early response data are also very promising.
Radio-labeling of MPDL3280A with the positron emission tomography (PET) radionuclide Zirconium-89 (89Zr) enables non-invasive imaging and quantification of PD-L1 distribution in cancer patients. By performing a 89Zr-MPDL3280A-PET scan prior to treatment with MPDL3280A, the uptake of the tracer in the primary and metastatic tumor lesions and normal organ distribution can be evaluated, as well as the use of a 89Zr-MPDL3280A-PET as a complementary tool for patient selection in the future.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02453984
|Contact: Elisabeth de Vries, Professoremail@example.com|
|Contact: Carolien Schroder, MDPhDfirstname.lastname@example.org|
|Principal Investigator:||Elisabeth de Vries, Professor||UMCG|