A recent clinical study (FIGHT-101) reported clinical efficacy and safety associated with selective FGFR 1-3 inhibitor, pemigatinib for advanced FGFR2-rearranged cholangiocarcinoma, and other cancers with alterations in FGFR. The results of this study were reported recently in the journal Annals of Oncology.
The phase1/II FIGHT-study enrolled unselected patients (n=128) with advanced malignancies, with or without alterations in fibroblast growth factor (FGF) and receptor (FGFR) to determine the recommended phase II dose (RP2D) and safety of selective FGFR 1-3 inhibitor, pemigatinib as monotherapy or in combination therapy. The first part (Part-1) of the study determined the maximum tolerated dose (MTD) of the inhibitor (dose escalation; 3+3 design). Further, the second part evaluated the recommended dosage of pemigatininb in tumours with FGF/FGFR activity.
Patients were administered pemigatinib (1-20mg) once daily (QD) either intermittently ( two-weeks on/one-week off; n=70) or continuously (n=58). Based on the MTD, pemigatinib was safe and tolerable with RP2D at 13.5 mg QD intermittent/continuous. The treatment-emergent adverse events were hyperphosphatemia (75.0%; grade ≥3, 2.3%) and fatigue (10.2%; grade ≥3). Dose interruption events occurred in 66 patients (51.6%), dose reduction in 14 patients (10.9%), and TEAE-related treatment discontinuation in 13 (10.2%) patients.
Partial responses (7.3 months [3.3-14.5], 95% confidence interval [CI]) were seen mostly in patients with cholangiocarcinoma (n=5) followed by head and neck, pancreatic, gallbladder, uterine, urothelial carcinoma, recurrent pilocytic astrocytoma, and non-small cell lung cancer (each n=1). Patients with FGFR fusion/rearrangements responded more to pemigatinib (n=5; 25.0% [95% CI, 8.7-49.1]) followed by thise with FGFR mutations (n=3; 23.1% [95% CI, 5.0-53.8]).
The phase I/II study demonstrated the safety and efficacy profile of pemigatinib across tumours with FGFR rearrangements/fusions and mutations.
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