Safety and Preliminary Evidence of Efficacy Shown for Rogaratinib

Inhibitors of the fibroblast growth factor receptors (FGFR) have shown promise in several cancers, but their effectiveness appears limited to cases with rare genetic FGFR aberrations. Schuler and colleagues report findings from an ongoing first-in-human phase I dose-escalation and dose-expansion study of the pan-FGFR inhibitor rogaratinib in 126 adults (91 [72%] male; 35 [28%] female) with advanced cancers. The dose-escalation phase involved 23 patients, and the dose-expansion phase involved 103 patients with tumors that overexpressed FGFR mRNA; these patients had urothelial carcinoma (52 patients), head and neck squamous cell carcinoma (8 patients), non–small cell lung cancer (20 patients), and other solid tumor types (23 patients). The primary endpoints were determination of safety and tolerability, maximum tolerated dose and dose-related toxicities, and recommended dose for a phase II trial. Fifteen of 100 evaluable patients (15%) had objective responses, as did 10 of 15 patients (67%) with FGFR-overexpressing tumors without any apparent genetic FGFR aberrations. Dose-limiting toxicities were not detected and the maximum tolerated dose was not reached. The most common adverse effects among all 126 patients were hyperphosphatemia (71 patients; 61%), diarrhea (65 patients; 52%), and decreased appetite (48 patients; 38%). Fatigue (11 patients; 9%) and asymptomatic increased lipase (10 patients; 8%) were the most common grade 3–4 adverse effects. Five patients exhibited severe adverse effects, including decreased appetite with diarrhea, acute kidney injury, hypoglycemia, retinopathy, and vomiting; six patients (all in the dose-expansion phase) permanently discontinued study treatment due to adverse effects. Of the 22 patients who died during the study or within 30 days of treatment discontinuation, no deaths were determined to be due to treatment. These results indicate that rogaratinib is safe, tolerable, and exhibits preliminary evidence of efficacy in a variety of cancer subtypes and suggest that FGFR mRNA expression level, in addition to FGFR mutation status, may be a useful biomarker for selecting patients for FGFR-inhibitor therapy.

Schuler M, Cho BC, Sayehli CM, Navarro A, Soo RA, Richly H, et al. Rogaratinib in patients with advanced cancers selected by FGFR mRNA expression: a phase 1 dose-escalation and dose-expansion study. Lancet Oncol 2019 Aug 9 [Epub ahead of print].

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