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FDA Approval Summary: Pemigatinib for Previously Treated, Unresectable Locally Advanced or Metastatic
Timil H Patel1, Leigh Marcus1, M Naomi Horiba1
1Office of Oncologic Diseases, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Abstract:
On April 17, 2020, the FDA granted accelerated approval to pemigatinib (PEMAZYRE, Incyte Corporation) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement as detected by an FDA-approved test. Approval was based on FIGHT-202 (NCT02924376), a multicenter open-label single-arm trial. Efficacy was based on 107 patients with locally advanced unresectable or metastatic cholangiocarcinoma whose disease had progressed on or after at least one prior therapy and had an FGFR2 gene fusion or rearrangement. Patients received pemigatinib, 13.5 mg orally, once daily for 14 consecutive days, followed by 7 days off therapy. Safety was based on a total of 466 patients, 146 of whom had cholangiocarcinoma and received the recommended dose. Efficacy endpoints were overall response rate (ORR) and duration of response (DOR) determined by an independent review committee using RECIST 1.1. ORR was 36% (95% confidence interval: 27-45). Median DOR was 9.1 months. The most common adverse reactions were hyperphosphatemia, alopecia, diarrhea, nail toxicity, fatigue, dysgeusia, nausea, constipation, stomatitis, dry eye, dry mouth, decreased appetite, vomiting, arthralgia, abdominal pain, hypophosphatemia, back pain, and dry skin. Ocular toxicity and hyperphosphatemia are important risks of pemigatinib. The recommended dosage is 13.5 mg orally once daily for 14 consecutive days followed by 7 days off therapy in 21-day cycles. FDA also approved the FoundationOne CDX (Foundation Medicine, Inc.) as a companion diagnostic for patient selection.
Insights
Pemigatinib (PEMAZYRE) offers a new treatment for advanced cholangiocarcinoma patients with FGFR2 rearrangements. This targeted therapy showed a 36% response rate and a median duration of response of 9.1 months in a clinical trial.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Cholangiocarcinoma is a rare and aggressive cancer.
- Fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements are key drivers in a subset of cholangiocarcinoma cases.
- Targeted therapies offer a promising avenue for patients with specific genetic alterations.
Purpose of the Study:
- To evaluate the efficacy and safety of pemigatinib in patients with previously treated, advanced cholangiocarcinoma harboring FGFR2 gene fusions or rearrangements.
- To determine the overall response rate (ORR) and duration of response (DOR) as primary efficacy endpoints.
- To assess the safety profile of pemigatinib in this patient population.
Main Methods:
- A multicenter, open-label, single-arm trial (FIGHT-202) was conducted.
- 107 patients with advanced cholangiocarcinoma and FGFR2 alterations, who progressed after prior therapy, were enrolled.
- Patients received pemigatinib 13.5 mg orally once daily for 14 days on/7 days off, with efficacy assessed by independent review.
Main Results:
- Pemigatinib demonstrated an ORR of 36% (95% CI: 27-45) in the efficacy-evaluable population.
- The median DOR was 9.1 months.
- Common adverse reactions included hyperphosphatemia, alopecia, diarrhea, and fatigue. Ocular toxicity and hyperphosphatemia are key risks.
Conclusions:
- Pemigatinib is an effective targeted therapy for patients with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements.
- The observed response rates and duration of response support its use in this indication.
- Close monitoring for adverse events, particularly hyperphosphatemia and ocular toxicity, is crucial.
