WASHINGTON – and reference tissue in an open-label, phase 1, first-in-human study.
The findings demonstrate the ability of the tracer–an anti-CD8 zirconium-labeled minibody–to noninvasively detect CD8 distribution in patients with metastatic solid tumors, potentially providing more information – and more quickly – than is possible with a single biopsy, Michael S. Gordon, MD, reported during a late-breaking abstract session at theof the Society for Immunotherapy of Cancer.
During a dose escalation period (stage 1) of the study, six patients received 3 mCi of 89Zr-IAB22M2C once intravenously followed by serial PET scans over a period of 5-7 days. The patients received increasing protein doses of 0.2 through 10 mg to establish safety and determine a “recommended protein dose and scanning parameters for subsequent trials,” explainedof HonorHealth Research Institute, Scottsdale, Ariz.
Stage 1 was followed by a dose expansion period (stage 2) in which an additional nine subjects were scanned to better delineate the recommended phase 2 study dose, he said.
All patients were monitored for drug-related adverse events and evaluated with blood chemistry, hematology, cytokine assay, and anti-drug antibodies. Biodistribution, radiodosimetry and semi-quantitative evaluation of CD8-tracer uptake were performed in all patients.
“We saw rapid clearance with excretion through the hepatobiliary mechanism, uptake in T-cell rich tissues, and no uptake in background normal tissues – so no uptake in muscle, heart, brain, or lungs,” he said, adding that “tumor uptake was variable and was clearly seen in 10 out of 15 patients.
“The protein dose that was considered to have favorable biodistribution was the range between 0.5 and 1.5, and based upon the analysis, the most favorable imaging time point ... was deemed to be 24 hours,” he said, noting that changes could be seen in as early as 6 hours.