Infigratinib a Novel, Potent Selective TKI Targeting FGFR Fusions in Different Tumor Types

June 2019, Vol 10, No 3

Atlanta, GA—Preclinical and clinical data support the potential for the investigational novel tyrosine kinase inhibitor (TKI) infigratinib for the treatment of different FGFR-driven tumor types, according to Sameek Roychowdhury, MD, PhD, Associate Professor, Medical Oncology, the Ohio State University, Columbus, who presented a poster with the preclinical results at the 2019 American Association for Cancer Research (AACR) meeting.

“Recent data show that fusion proteins involving FGFR have been identified in a diverse range of solid tumors, including lung, breast, thyroid, and prostate cancers, as well as cholangiocarcinoma and bladder cancer,” said Dr Roychowdhury at the AACR meeting.

“Given the fact that scientists are identifying more tumor types driven by mutations in FGFRs, it expands the potential for a compound like infigratinib as an effective treatment for many more cancers than previously understood,” Dr Roychowdhury said.

Infigratinib is an oral investigational potent and selective TKI targeting FGFR1, FGFR2, and FGFR3, in FGFR fusion–positive cholangiocarcinoma, and these mutations are present in other solid tumors as well.

Researchers identified patients with FGFR fusions and developed patient-derived xenograft models to ascertain the effect of infigratinib treatment. Specifically, they studied xenograft models of cholangiocarcinoma, breast cancer, liver cancer, gastric cancer, and glioma, which showed that treatment with infigratinib resulted in a reduction in tumor volume in all samples compared with inactive treatment.

New FGFR fusions continue to be identified in multiple tumor types, expanding the potential applicability of this novel selective TKI. For example, the researchers identified and characterized a novel FGFR fusion in prostate cancer.

In addition, an open-label phase 2 clinical trial showed that infigratinib achieved a confirmed overall response rate of 39.3% in patients with FGFR2 fusion–positive cholangiocarcinoma who received treatment with this novel agent as a second-line therapy. Infigratinib also achieved clinical benefit in noncholangiocarcinoma tumors that tested positive for FGFR fusions.

“While previously presented data have shown the promise of infigratinib for the treatment of cholangiocarcinoma and urothelial carcinoma, these data provide a clear rationale for performing tumor-agnostic clinical trials across all molecularly defined solid tumors,” said Gary Li, PhD, lead author of the study and Senior Vice President, Translational Medicine, QED Therapeutics, San Francisco, CA.

If future studies confirm the benefit of infigratinib in FGFR-driven tumors in any site, this selective TKI would join the list of other novel agents targeting different gene mutations, such as alectinib (Alecensa) for ALK-driven lung cancers, gilteritinib (Xospata) for FLT3-positive acute myeloid leukemia, and lorlatinib (Lorbrena) targeted to ROS1 rearrangements.

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