FDA Grants Priority Review to Pemigatinib for FGFR2+ Cholangiocarcinoma


The FDA has granted a priority review to the agent pemigatinib for patients with previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements.

The FDA has granted a priority review to a new drug application (NDA) for pemigatinib as a treatment for patients with previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements.1

The designation is based on interim findings from the multicohort, single-arm, phase II FIGHT-202 study, which showed that, at a median follow-up of 15 months, single-agent pemigatinib led to a 36% objective response rate (ORR) and a median duration of response of 7.5 months in a cohort of patients with FGFR2 fusions or rearrangements.2 The selective inhibitor of FGFR1, 2, and 3 was also associated with a manageable adverse event (AE) profile.

“There is a significant need for new therapies for patients with cholangiocarcinoma, who have limited treatment options beyond first-line chemotherapy and often face a poor prognosis,” Peter Langmuir, MD, Group Vice President of Targeted Therapeutics at Incyte, the developer of pemigatinib, stated in a press release.

Patients with cholangiocarcinoma are often diagnosed at a late or advanced stage when the prognosis is poor, Incyte stated in the press release.

While first-line treatment for patients with locally advanced or metastatic cholangiocarcinoma is the chemotherapy combination of gemcitabine and cisplatin, second-line therapies have shown limited efficacy.

The FIGHT-202 trial was conducted in the United States, Europe, Middle East, and Asia. Patients who were eligible for enrollment had locally advanced or metastatic cholangiocarcinoma despite ≥1 line of prior therapy, had their FGF/FGFR status centrally confirmed, and adequate renal function was required.

Patients were stratified into 3 cohorts: those with FGFR2 fusions/rearrangements (cohort A; n = 107), those with other FGF/FGFR genetic alterations (cohort B; n = 20), and no FGF/FGFR alterations (cohort C; n = 18). Patients in each of the 3 cohorts were treated with oral pemigatinib (13.5 mg) using a 2-weeks-on/1-week-off schedule.

The study was not designed to make statistical comparisons between the 3 cohorts. The primary endpoint was the confirmed ORR in cohort A by independent central review.

Among the 107 patients in cohort A, 92 fusions and 15 rearrangements identified. A total of 56 unique fusion partners were identified, the most common of which was BICC1, which occurred in 29%. Forty-two partners were unique to a single patient, and no fusion partner was identified in 5% of patients.

Results showed that, in cohort A, the 36% ORR consisted of 3 (2.8%) complete responses, 35 (32.7%) partial responses, and 50 (46.7%) patients with stable disease, for a disease control rate of 82%. The ORR was consistent across subgroups, including when stratified by the number of prior lines of therapy and by FGFR2 rearrangement partner.

Additionally, the higher ORR translated into a longer median progression-free survival (PFS) in cohort A. Median PFS was 6.9 months in cohort A compared with 2.1 months in cohort B and 1.7 months in cohort C.

Overall survival (OS) data were not yet mature at the time of the March 22, 2019, data cutoff. However, but with a median duration of follow-up of 15.4 months and a median duration of treatment of 7.2 months, the median OS was 21.1 months in the cohort with FGFR2 fusions/rearrangements. Median OS was only 6.7 months in the cohort with other FGF/FGFR alterations after a median follow-up of 19.9 months, and only 4.0 months in the cohort without an FGF/FGFR alteration after a median follow-up of 24.2 months.

Regarding safety, AEs were found to be manageable and consistent with the mechanism of action of pemigatinib. The most common AE was hyperphosphatemia (60%), but no grade ≥3 cases were encountered. Hyperphosphatemia was managed with a low phosphate diet, phosphate binders, diuretics, and a reduction or interruption in the pemigatinib dose. Three patients required dose reductions/interruptions due to hyperphosphatemia.

Any-grade hypophosphatemia occurred in 23% of patients and was the most common grade ≥3 AE, with a rate of 12%. No case of hypophosphatemia was clinically significant, and none led to treatment discontinuation or dose reduction. Serous retinal detachment occurred in 4% of patients and usually resolved spontaneously or after dose interruption.

Nine percent of patients discontinued due to AEs; the most frequent causes were intestinal obstruction and acute kidney injury (2 each). Treatment was discontinued due to progressive disease in all patients in cohorts B and C, and in 57 patients in cohort A. Dose reduction due to AEs was required in 14%, with the most common reasons being stomatitis (n = 11), palmar-plantar erythrodysesthesia syndrome (n = 5), arthralgia (n = 5), asthenia (n = 2), and onychomadesis (n = 2). Approximately 42% of patients required dose interruptions due to AEs.

Based on the data from FIGHT-202, a phase III study of pemigatinib compared with gemcitabine plus cisplatin in the first-line setting in patients with cholangiocarcinoma and FGFR2 fusions/rearrangements is ongoing (NCT03656536).

This article originally appeared in OncLive® as, “FDA Grants Priority Review to Pemigatinib for FGFR2+ Cholangiocarcinoma


  • Incyte Announces Acceptance and Priority Review of NDA for Pemigatinib as a Treatment for Patients with Cholangiocarcinoma. Incyte. Published November 27, 2019. https://bit.ly/35KAHZf. Accessed November 27, 2019.
  • Hollebecque A, Borad M, Sahai V, et al. FIGHT-202: a phase 2 study of pemigatinib in patients (pts) with previously treated locally advanced or metastatic cholangiocarcinoma (CCA). Presented at: 2019 ESMO Congress; September 27-October 1, 2019; Barcelona, Spain. Abstract LBA40.

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