FDA Approves Pemigatinib for FGFR2+ Cholangiocarcinoma

The FDA has approved pemigatinib for the treatment of adult patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 fusion or rearrangement.

The FDA has approved pemigatinib (Pemazyre) for the treatment of adult patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 fusion or rearrangement, as detected by an FDA-approved test.1

This represents the first approved treatment for this indication.

Approval for pemigatinib, a selective oral inhibitor of FGFR1, 2, and 3, was accelerated and is contingent upon confirmatory trial(s).

“Although cholangiocarcinoma is considered a rare disease, it has been on the rise over the past three decades,” said study investigator Ghassan Abou-Alfa, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, in a statement. “It is encouraging to have a new targeted treatment option for patients who historically have had limited options after first-line chemotherapy or surgery, in which relapse rates remain high.”

Findings from cohort A of the phase II FIGHT-202 trial supported the approval showing an overall response rate of 36% and a median duration of response of 9.1 months.

FIGHT-202 is a multi-center, open-label, single-arm study that investigated the use of pemigatinib in patients with locally advanced, metastatic, or unresectable cholangiocarcinoma who had failed at least 1 prior therapy (NCT02924376). Patients were enrolled into 1 of 3 cohorts: cohort A included patients with FGFR2 fusions or rearrangements, cohort B included patients with FGF/FGFR genetic alterations, and cohort C included those with no FGF/FGFR genetic alterations.

Eligible patients included those with histologically or cytologically confirmed cholangiocarcinoma, measurable or evaluable disease, disease progression after at least 1 prior systemic treatment, an ECOG performance status score of 0 to 2, and a life expectancy of at least 12 weeks. Exclusion criteria included prior use of a selective FGFR inhibitor, evidence of current or prior ectopic mineralization/calcification, clinically significant corneal or retinal disorder, and recent use of a CYP3A4 inhibitor.

Patients across the 3 cohorts received oral pemigatinib at 13.5 mg daily in a 2-weeks-on and 1-week-off schedule until disease progression, unacceptable toxicity, withdrawal of consent, or physician decision.

The primary end point of the trial was the objective response rate (ORR) in cohort A. Secondary outcome measures included ORR in the other cohorts, progression-free survival (PFS), and safety.

A total of 107 patients were treated in cohort A and followed for a median of 15.4 months (range, 9.3-19.0). The median duration of treatment was 7.2 months (range, 3.9-10.9).2

Patients in the cohort had a median age of 56 years (range, 26-77) and 61% were female. The majority of patients had metastatic disease (82%) and an ECOG performance status score of 1 (53%). Sixty-one percent of patients had only received 1 prior line of therapy, whereas 12% had received at least 3. Additionally, 36% had undergone prior surgery and 26% had received radiotherapy. Ninety-eight percent of patients had intrahepatic cholangiocarcinoma, and the most common site of disease was the liver (94%).

The most common FGFR2 partner gene reported was BICC1 in 29% of patients. Forty-two patients had FGFR2 partner genes that were unique to them, but a total of 56 different partners were reported.

By the time of data cutoff, 71% of patients had discontinued treatment, most often due to progressive disease (55%).

Confirmed complete responses were observed in 2.8% of patients and partial responses in 32.7%; a total of 82% of patients achieved disease control. Eighty-eight percent saw reductions in target lesion size from baseline.

The median PFS was 6.9 months (95% CI, 6.2-9.6), and although not fully mature at the time of cutoff, the median overall survival was 21.1 months (95% CI, 14.8 to not estimable).  

No patients in cohort B or C achieved a response.

In the total patient population, the most common adverse event (AE) was hyperphosphatemia in 60% of patients, followed by alopecia (46%), dysgeusia (38%), diarrhea (34%), and fatigue (31%).

Hyperphosphatemia had a median onset time of 15 days (95% CI, 8-47), which was managed with a low-phosphate diet, concomitant phosphate binders, diuretics, dose reduction, or dose interruption.

The most frequent grade 3 or higher AEs were hypophosphatemia (12%), arthralgia (6%), stomatitis (5%), hyponatremia (5%), abdominal pain (5%), and fatigue (5%).

Serious AEs were observed in 45% of patients, including abdominal pain, pyrexia, cholangitis, and pleural effusion. Forty-nine percent of all patients died on trial, most frequently due to disease progression. Six patients died from treatment-emergent AEs, including failure to thrive in 2 patients and bile duct obstruction, sepsis, pleural effusion, and cholangitis in 1 patient each.

Warnings and precautions for pemigatinib include eye problems, high levels of phosphate in the blood, and a risk of fetal harm or loss of pregnancy for pregnant women.

The FDA simultaneously approved FoundationOne CDx as the registrational companion diagnostic for identifying patients who may benefit from pemigatinib. This is the first and only FDA-approved companion diagnostic test for the use of pemigatinib as a treatment of patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement.3

The FDA previously granted pemigatinib a breakthrough and orphan drug designation for this indication.

“Our research into FGFR2 fusions or rearrangements in cholangiocarcinoma and the development of Pemazyre as the first targeted treatment option demonstrates our commitment to translating scientific discovery into solutions that can positively impact patients’ lives,” said Hervé Hoppenot, CEO of Incyte, in a statement. “We’re proud to bring Pemazyre to patients and will make this new treatment available immediately.”

Incyte is providing access to a comprehensive patient support program for all patients who receive pemigatinib.


  1. FDA Approves Incyte’s Pemazyre™ (pemigatinib) as First Targeted Treatment for Adults with Previously Treated, Unresectable Locally Advanced or Metastatic Cholangiocarcinoma [news release]. Wilmington, DE: Incyte; April 17, 2020. https://bwnews.pr/3bvVgLW. Accessed April 18, 2020.
  2. Abou-Alfa GK, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study [published online March 20, 2020]. Lancet Oncol. doi: 10.1016/S1470-2045(20)30109-1.
  3. Foundation Medicine Receives FDA Approval for FoundationOne®CDx as the Companion Diagnostic for Pemazyre™ (pemigatinib), the First FDA-Approved Targeted Therapy for Adults with Previously Treated Locally Advanced or Metastatic Cholangiocarcinoma [news release]. Cambridge, MA: Foundation Medicine; April 17, 2020. https://bwnews.pr/2RM45tx. Accessed April 18, 2020.