Pemazyre (pemigatinib) is a kinase inhibitor.
Pemazyre is specifically indicated 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.
Pemazyre is supplied as a tablet for oral administration. The recommended dosage of Pemazyre is 13.5 mg orally once daily for 14 consecutive days followed by 7 days off therapy, in 21-day cycles. Continue treatment until disease progression or unacceptable toxicity occurs. Take Pemazyre with or without food at approximately the same time every day. Swallow tablets whole. Do not crush, chew, split, or dissolve tablets. If the patient misses a dose of Pemazyre by 4 or more hours or if vomiting occurs, resume dosing with the next scheduled dose.
Pemazyre was approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
The FDA approval of Pemazyre was based on data from FIGHT-202, a multi-center, open-label, single-arm study in adult (age ≥18 years) patients with previously treated, locally advanced or metastatic cholangiocarcinoma with documented FGFR2 fusion or rearrangement. Patients were enrolled into one of three cohorts – Cohort A (FGFR2 fusions or rearrangements), Cohort B (other FGF/FGFR genetic alterations) or Cohort C (no FGF/FGFR genetic alterations). All patients received 13.5 mg Pemazyre orally once daily (QD) on a 21-day cycle (two weeks on/one week off) until radiological disease progression or unacceptable toxicity. The primary endpoint of FIGHT-202 was overall response rate (ORR) in Cohort A, assessed by independent review per RECIST v1.1. Secondary endpoints included duration of response (DOR). In patients harboring FGFR2 fusions or rearrangements (Cohort A), Pemazyre monotherapy resulted in an overall response rate of 36% and median DOR of 9.1 months.
Adverse effects associated with the use of Pemazyre may include, but are not limited to, the following:
Pemazyre (pemigatinib) is a small molecule kinase inhibitor that targets FGFR1, 2 and 3 with IC50 values of less than 2 nM. Pemigatinib also inhibited FGFR4 in vitro at a concentration approximately 100 times higher than those that inhibit FGFR1, 2, and 3. Pemigatinib inhibited FGFR1-3 phosphorylation and signaling and decreased cell viability in cancer cell lines with activating FGFR amplifications and fusions that resulted in constitutive activation of FGFR signaling. Constitutive FGFR signaling can support the proliferation and survival of malignant cells. Pemigatinib exhibited anti-tumor activity in mouse xenograft models of human tumors with FGFR1, FGFR2, or FGFR3 alterations resulting in constitutive FGFR activation including a patient-derived xenograft model of cholangiocarcinoma that expressed an oncogenic FGFR2Transformer-2 beta homolog (TRA2b) fusion protein.
For additional information regarding Pemazyre or previously treated, unresectable locally advanced or metastatic FGFR2 positive cholangiocarcinoma, please visit the Pemazyre website.