NCT05742269

Molecular PD-L1 PET/CT Imaging With 89Zr-atezolizumab in Metastatic Triple Negative Breast Cancer

Molecular PD-L1 PET/CT Imaging With 89Zr-atezolizumab to Monitor Immune Responses in Metastatic Triple Negative Breast Cancer

• Status: Terminated
• Phase: —
• Study type: Observational
• Enrollment: 3 (actual)
• Sponsor: Karolinska University Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The overarching purpose of this study is to improve precision medicine through more refined therapy selection for breast cancer patients who are candidates for ICI therapy (monoclonal antibodies targeting the programmed death ligand 1 (PD-L1) or programmed cell death protein 1 (PD-1)). The reference standard biomarker for ICI therapy selection is PD-L1 protein expression measured by immunohistochemistry (IHC). Several disadvantages exist with this method, the most important ones being inter- and intralesional as well as spatial heterogeneity in PD-L1 expression, as well as the need for invasive procedures to obtain material for analysis. The study hypothesis is that Positron Emission Tomography combined with Computed Tomography (PET/CT) imaging with a contemporary radiotracer (89Zr-atezolizumab), visualizing PD-L1 expression in the whole body, could be a better predictive biomarker to select which patients benefit from ICI. The use of PET/CT imaging with new radiotracers enables a non-invasive assessment of the presence of the target of treatment in the whole body and provides the possibility to combine functional information with anatomical details.

Detailed description

Patients with mTNBC scheduled for first line palliative systemic treatment with nab-paclitaxel and carboplatin can be included. This chemotherapy combination is used to maximize the therapeutic potential of this first line systemic treatment line, extrapolating signals from early TNBC and in the absence of signs that indicate augmented safety issues. The investigational medical product is 89Zr-atezolizumab. The pharmaceutical preparation of the IMP consists of the precursor atezolizumab combined with zirconium-89 to form 89Zr-atezolizumab. The radiolabelling of atezolizumab will be performed at the Department of Radiopharmacy, Karolinska University Hospital, Solna. This involves an automated synthesis procedure in a Good Manufacturing Practice facility. All patients are scheduled for treatment with nab-paclitaxel at a dose of 100 mg per square meter of body-surface area, administered intravenously, on days 1, 8, and 15, and carboplatin at a dose of Area Under the Curve (AUC) 5 on day 1 of every 28-day cycle. The patients with a PD-L1+ tumour according to IHC with the SP142 antibody (≥ 1% on immune cells) and/or 89Zr-atezolizumab tracer uptake on PET-imaging, will receive atezolizumab at a dose of 840 mg, administered intravenously, on days 1 and 15.

Conditions

• Metastatic Triple-Negative Breast Carcinoma

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	89Zr-atezolizumab PET/CT	All patients undergo a 89Zr-atezolizumab PET/CT. Allocation to chemotherapy + atezolizumab in case of a PD-L1 positive tumor (on IHC and/or PET)

Timeline

• Start date: 2023-07-01
• Primary completion: 2024-12-01
• Completion: 2026-03-11
• First posted: 2023-02-23
• Last updated: 2026-03-13

Locations

1 site across 1 country: Sweden