On April 17, the U.S. Food and Drug Administration (FDA) granted accelerated approval to pemigatinib (Pemazyre) for the treatment of adult patients 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.
The FDA also approved the FoundationOne CDX as a companion diagnostic for patient selection.
Efficacy was investigated in FIGHT-202, a multicenter, open-label, single-arm trial. The study included 107 patients with locally advanced unresectable or metastatic cholangiocarcinoma and an FGFR2 gene fusion or rearrangement (clinical trial assay performed at a central laboratory) whose disease had progressed on or after at least one prior therapy. Patients received oral pemigatinib at 13.5 mg once daily for 14 consecutive days, followed by 7 days off therapy.
The major efficacy outcome measures were overall response rate and duration of response as determined by an independent review committee using Response Evaluation Criteria in Solid Tumors, version 1.1.
Among the 107 patients, the overall response rate was 36% (95% confidence interval [CI] = 27%–45%), including three complete responses. The median duration of response was 9.1 months, with responses lasting ≥ 6 months in 24 of the 38 (63%) responding patients and ≥ 12 months in 7 of the 39 (18%) patients.
The most common adverse reactions to pemigatinib (incidence ≥ 20%) 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.
The recommended pemigatinib dose is 13.5 mg orally once daily for 14 consecutive days followed by 7 days off therapy in 21-day cycles.
Richard Pazdur, MD
“This approval demonstrates that while we continue to focus our efforts on addressing the COVID-19 pandemic, the FDA remains committed to the important work of reviewing treatments for patients with cancer and other serious conditions,” said 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. “With pemigatinib, 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.”