A pilot study of Positron Emission Tomography (PET) scanning with 89Zr-DFO-Atezolizumab in patients receiving pembrolizumab for non-small cell lung cancer

Background Lung cancer affects over 45,000 people per year in the UK with a 19% one-year survival for those with metastatic disease. In non-small cell lung cancer (NSCLC) immune checkpoint inhibitors (ICIPs/immunotherapy) are standard of care.

NSCLC patients receive chemotherapy or ICIPs (e.g pembrolizumab) or chemotherapy-pembrolizumab combination depending on the baseline tumoural (biopsy) PD-L1 results.

Tumoural PD-L1 is not a perfect biomarker of response with around 50% of patients expected to not respond to ICPI using this method of patient selection.

ICPI carries a burden of toxicity with immune activation causing debilitating and potentially life-threatening toxicities.

FDG-PET (Positon Emission Tomography) scanning utilises a radiolabelled tracer to give a read-out of metabolic cancer activity and, in combination with simultaneously acquired CT (computer tomography) images is a adjunct to response assessment. PET imaging with alternative labelled tracers is feasible.

Immuno-PET with radiolabelled monoclonal antibodies (mAbs) to PD-L1 could enable a quantitative read out of the checkpoints on tumour and other cells (e.g. tumour-associated macrophages) and sequential measurements of PD-L1 expression over time without a need of repeated biopsies Aims We postulate that radio-labelled atezolizumab (89Zr-DFO-Atezolizumab) will provide a non-invasive and quantifiable measure of PD-L1 expression level that can ultimately become a biomarker for patient selection.

Methods This single centre study of 10 patients with NSCLC receiving pembrolizumab as part of their standard of care. Patients will have a baseline 89Zr-DFO-Atezolizumab scan in the two weeks prior to commencing pembrolizumab. Scans will be repeated at 9 weeks and at progression.

For each administration of 89Zr-DFO-Atezolizumab (37 MBq), imaging will be performed at 2 days and 4 days post-injection.

The sub-therapeutic administration of the radiolabelled atezolizumab is considered to be safe and have low toxicity risk. The primary end-point is description of baseline SUV (PET read-out).

Secondary end-points include comparison with baseline tumoural PD-L1, change in PET characteristics over time and against radiological response.

How results will be used The following step is to use the PET read-out to change patient treatment decisions and relies on the results of clinical trials in which patients are randomised to ICIP trials on the PET results. Ultimately, implementation in the NHS will use existing PET imaging infrastructure and existing radiologist expertise.

The cost of a PET CT scan is around £650 per scan.

Given pembrolizumab costs £5260 per 3 weekly treatment the cost-benefit of an implementation that improves patient selection is likely to be large.