The Food and Drug Administration (FDA) has granted accelerated approval of Pemazyre™ (pemigatinib; Incyte) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.
Pemigatinib, a small molecule kinase inhibitor, selectively targets FGFR isoforms 1, 2 and 3, which, in preclinical studies, has resulted in anti-tumor activity in cells with FGFR alterations. The approval was based on data from the multicenter, open-label, single-arm phase 2 FIGHT-202 study that evaluated the efficacy and safety of pemigatinib in 107 adult patients with locally advanced unresectable or metastatic cholangiocarcinoma with FGFR2 translocation who have failed at least 1 previous treatment. Patients received pemigatinib orally once daily on a 21-day cycle (14 days on/7 days off) until disease progression or unacceptable toxicity.
The primary end point was the overall response rate (ORR) based on RECIST v1.1, defined as the proportion of patients who achieved a complete or partial response (≥30% decrease in the sum of the longest diameters of target lesions); a key secondary end point included the duration of response (DoR).
Results showed that treatment with pemigatinib was associated with an ORR of 36% (n=38; 95% CI, 27-45), with 2.8% of patients having a complete response and 33% having a partial response. Among the 38 patients who had a response, the median DoR was 9.1 months (95% CI, 6.0-14.5), with 24 patients (63%) having a response of ≥6 months and 7 patients (18%) having a response of ≥12 months.
With regard to safety, the most common adverse reactions observed 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. In addition, among the 466 patients who received pemigatinib across clinical trials, 6% of patients developed retinal pigment epithelial detachment.
Commenting on the approval, Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said: “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.”
Pemazyre is available as 4.5mg, 9mg, and 13.5mg tablets in 14-count bottles. It will be dispensed exclusively by Biologics by McKesson specialty pharmacy.
For more information visit pemazyre.com.