Dr. Roychowdhury on FGFR Inhibitor Infigratinib in Cholangiocarcinoma

Sameek Roychowdhury, MD, PhD, associate professor of medical oncology, the Ohio State University Comprehensive Cancer Center, discusses a phase II study with infigratinib (BGJ398) in patients with cholangiocarcinoma.

Infigratinib (BGJ398) is a selective FGFR inhibitor under investigation in the space, says Roychowdhury. With pre-treatment and post-progression biopsy, investigators have been able to look at acquired mechanisms of resistance in patients with cholangiocarcinoma. Melanie Krook, a postdoctoral researcher with a focus on FGFR drug resistance, was able to demonstrate that the acquisition of new mutations in FGFR did not confer resistance to infigratinib.

In a poster presentation at the 2019 AACR Annual Meeting, Krook explained how she was able to examine protein data as well as in cells that had been transfected with these mutations. Investigators could see that activation of other pathways could render cells sensitive to combination with infigratinib plus either an MTOR or AKT inhibitor. Roychowdhury says that combination therapy could be a potential avenue to pursue down the road after clinical studies exploring the use of single-agent therapies conclude.

The next step for this research is to pool the data from this study and others to gain a better understanding of the overall landscape of FGFR resistance among patients with cholangiocarcinoma. What are all of the mechanisms that can be catalogued? According to Roychowdhury, this information will help inform drug development.

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