The FGFR Inhibitor BGJ398 Has Activity in Tumors with FGFR Alterations

Activating genomic alterations in the fibroblast growth factor receptor (FGFR) occur in multiple tumor types including bladder cancer, squamous cell non–small cell lung cancer (sqNSCLC), cholangiocarcinomas, and breast cancer. An orally bioavailable FGFR-selective tyrosine kinase inhibitor (TKI), BGJ398, has been shown to reduce tumor growth in FGFR-altered preclinical tumor models, but no FGFR-selective TKIs have been approved for clinical use. Nogova and colleagues tested BGJ398 in a phase I single-agent dose escalation and dose-expansion study in 132 patients with advanced solid tumors with alterations in FGFR, such as amplifications, mutations, or fusions. The primary objective was to determine the maximum tolerated dose, recommended phase II dose, and schedule of oral BGJ398. Secondary objectives included determining the safety, tolerability, and antitumor activity of BGJ398. At the determined recommended dose, BGJ398 was tolerable and had a manageable toxicity. Compared with continuous treatment, patients treated on an intermittent 3-weeks-on/1-week-off schedule experienced fewer adverse events that required dose adjustments or interruptions. Partial responses were achieved in 7 patients, 4 with sqNSCLC and 3 with bladder/urothelial cancer, and stable disease was observed in an additional 42 patients. A reduced tumor burden was observed in 28 of the 85 (32.9%) evaluable patients treated with at least 100 mg BGJ398. Notably, 18 of 36 patients with sqNSCLC, 6 of 8 patients with bladder/urothelial cancer, and 10 of 32 patients with breast cancer treated with at least 100 mg of BGJ398 achieved disease control. In addition, all 3 patients with cholangiocarcinomas experienced a reduction in tumor burden. The results of this phase I trial suggest that BGJ398 has antitumor activity and an acceptable safety and tolerability at the determined recommended dose in patients with FGFR-altered tumors, and support its further clinical investigation, especially in patients with sqNSCLC or bladder/urothelial cancer.

Nogova L, Sequist LV, Perez Garcia JM, Andre F, Delord JP, Hidalgo M, et al. Evaluation of BGJ398, a fibroblast growth factor receptor 1-3 kinase inhibitor, in patients with advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors: results of a global phase I, dose-escalation and dose-expansion study. J Clin Oncol 2016 Nov 21 [Epub ahead of print].

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