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WASHINGTON -- The fibroblast growth factor receptor (FGFR) inhibitor pemigatinib (Pemazyre) received the for cholangiocarcinoma associated with FGFR-2 gene fusions or certain other rearrangements.

The accelerated approval specifies pemigatinib for patients with previously treated, locally advanced disease and requires confirmatory studies for final approval. Most patients affected by cholangiocarcinoma, or cancer of the bile ducts, have advanced, unresectable disease at diagnosis. Until now, no approved therapies existed for the condition. Empiric treatment with chemotherapy has resulted in response rates of 9-14%.

"With Pemazyre, we considered the observed efficacy results to be clinically meaningful and the overall risk to benefit assessment for patients with tumors harboring FGFR2 gene fusions and other rearrangements to be favorable, particularly when we considered that these patients have no other good options, following first-line treatment with chemotherapy," according to a statement from Richard Pazdur, MD, of the FDA Office of Oncologic Diseases.

The principal supporting evidence for the approval came from the phase II, open-label , which included 146 patients with previously treated, locally advanced or metastatic cholangiosarcoma (107 with FGFR2 rearrangements/fusions, 20 with miscellaneous FGF/FGFR aberrations, 18 without gene alterations, and one unknown). The trial had a primary endpoint of objective response rate, which proved to be 35.5% in the overall population (including three complete responses).

Responses occurred only in patients with FGFR2 rearrangements or fusions. Almost two thirds of responses (24 of 38) lasted 6 months or longer and seven responses persisted for 12 months or beyond.

Other key endpoints of the trial included:

• Median duration of response -- 7.5 months

• Disease control rate -- 82%

• Median progression-free survival -- 6.9 months

• Median overall survival -- 21.1 months

The most common adverse events were hyperphosphatemia (60%, 3% grade ≥3), fatigue (42%, 5%), nail toxicities (42%, 2%), and dysgeusia (40%, 0%). Discontinuation, dose reduction, and dose interruption related to adverse events occurred in 9%, 14%, and 42% of patients, respectively.

The FDA granted the accelerated approval to Innovent Biologics. The FIGHT-202 trial was supported by Incyte, which entered into a clinical development collaboration with Innovent in 2018.

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