On October 8, 2016, results of the first-in-human dose escalation study of the pan-FGFR (fibroblast growth factor receptor) inhibitor BAY 1163877 in patients with treatment-refractory locally advanced or metastatic solid tumors were reported today at the ESMO 2016 Congress in Copenhagen. The novel compound uses messenger RNA (mRNA) in tumors to identify patients who will respond. "Most studies of FGFR inhibitors have looked at FGFR abnormalities in tumors with limited success," said lead author Dr Markus Joerger, attending medical oncologist, St Gallen Cancer Centre, Switzerland. "This study used an innovative biomarker approach of tumor FGFR mRNA expression." This multicenter phase I study was conducted in six countries. The dose-escalation study was followed by expansion cohorts in patients with high tumor FGFR mRNA levels. A total of 80 patients were enrolled and treated, including 23 patients in the dose-escalation phase and 57 patients in the expansion cohorts in bladder cancer, head and neck cancer, lung cancer, and all comers. The dose escalation study tested five doses ranging from 50-800 mg BID (twice daily). BAY 1163877 has a half-life of about 12 hours and revealed less than dose-proportional increase in exposure at doses above 200 mg. A maximum tolerated dose was not defined because there were no dose-limiting toxicities. Based on the results of preclinical studies, the effect on serum phosphate levels and clinical analyses, 800 mg BID was recommended for future study. Regarding toxicities, most patients developed low-grade hyperphosphatemia, which occurs with all FGFR inhibitors. These patients were given a phosphate binder and the dose of BAY 1163877 could be reduced to avoid further increases of phosphate levels in the blood.
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