Use of 18F-HX4 PET/CT to Estimate Tumor Hypoxia Enrolled Subjects from Ongoing Phase 2 Trials Using Tarloxotinib Bromide in Advanced NSCLC and SCCHN.

e23158 Background: Tumor hypoxia is associated with resistance to chemotherapy and radiotherapy. Recurrent/metastatic squamous cell carcinomas of the head and neck & skin (SCCHN/SCCS) and non-small cell lung cancer (NSCLC) tumors can be hypoxic leading to EGFR-TKI resistance. Tarloxotinib bromide (TRLX) is a hypoxia-activated prodrug that releases an irreversible pan-ErbB TKI targeting WT EGFR, mutant EGFR and HER2. Hypoxic tumor targeting with TRLX may lead to greater TKI tumor exposure with less toxicity than current EGFR TKIs. 18F-flortanidazole (18F-HX4) is a new hypoxia PET imaging agent that has the potential to identify and quantify tumor hypoxia with better tumor hypoxia targeting than earlier PET hypoxia agents. However, cross-institutional comparison of PET results without a standardization program can be challenging leading to insufficient or inappropriate conclusions based on PET results. Methods: Two concurrent multicenter Phase 2 trials are investigating the safety and activity of single-agent TRLX in recurrent or recurrent/metastatic SCCHN and SCCS (NCT02449681) or NSCLC (NCT02454842). Subjects have a whole-body18F-HX4 PET/CT scan prior to treatment. PET scanners are prequalified using a phantom harmonization program to ensure consistent image quality and robust 18F-HX4 quantitation for cross-institutional comparison. 18F-HX4 uptake will be quantitated to help correlate tumor 18F-HX4 uptake with measurement-based tumor treatment responses. Results: Up to 4 sites have been qualified with anthropomorphic phantoms to standardize PET scans and avoid poor quantitation of 18F-HX4. Excellent image quality scans in 3 of 4 patients have shown 18F-HX4 tumor uptake with preliminary estimates of tumor hypoxia ranging from 0-21% for hypoxic fractions (% of tumor hypoxia relative to reference tissue) and volumes (volume of hypoxia relative to reference tissue) permitting feasibility of signal detection to be correlated with responses. Conclusions: Multicenter PET studies of 18F-HX4 uptake and tumor response to TRLX is ongoing. Our PET harmonization strategy has shown promising early results in tumor hypoxia visualization. Recruitment is ongoing. Clinical trial information: NCT02449681.