Pemigatinib — Drug Monograph

Brand names: Pemazyre

Drug class: Tyrosine Kinase Inhibitor

Mechanism of Action

Selective, potent, reversible (non-covalent) inhibitor of fibroblast growth factor receptors 1, 2, and 3 (FGFR1/2/3). Cholangiocarcinoma — particularly intrahepatic (iCCA) — harbors FGFR2 fusions and rearrangements in approximately 10–15% of cases, which cause constitutive FGFR2 kinase activation driving RAS/MAPK, PI3K/AKT, and STAT signaling. Pemigatinib blocks FGFR1/2/3 ATP-binding sites, suppressing downstream proliferative and survival signaling, inducing apoptosis in FGFR2-fusion–driven tumor cells. Also inhibits FGFR1 and FGFR3, contributing to activity in hematologic malignancies with…

FDA Indications

• Previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with FGFR2 fusion or rearrangement (FDA approved April 2020 — FIGHT-202 Phase 2: ORR 35.5%, median PFS 6.9 months)
• Relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangement (FDA approved August 2022 — FIGHT-203: complete hematologic response 78%)

Common Side Effects

• Hyperphosphatemia (>80% — nearly universal; class effect of FGFR inhibitors)
• Alopecia (49%)
• Diarrhea (47%)
• Nail toxicity (onycholysis, paronychia — 44%)
• Fatigue (42%)
• Stomatitis / mucositis (39%)
• Dry eye / eye disorders (35%)
• Arthralgia / musculoskeletal pain
• Dry skin
• Nausea and constipation

Clinical Pearl

Hyperphosphatemia is essentially universal (>80%) with pemigatinib and is a class effect of FGFR inhibitors due to direct inhibition of renal FGF23 signaling (FGF23 normally promotes phosphate excretion). Phosphate levels must be monitored monthly and managed proactively with dietary restriction and phosphate binders. Ocular toxicity (CSR/RPED) is a mandatory monitoring concern requiring ophthalmologic follow-up every 2 months. Futibatinib (irreversible covalent FGFR1-4 inhibitor) retains…

Related Therapies & Mechanisms

• Afatinib (Gilotrif) — Tyrosine Kinase Inhibitor
• Alectinib (Alecensa) — Tyrosine Kinase Inhibitor
• Alpelisib (Piqray) — Tyrosine Kinase Inhibitor
• Asciminib (Scemblix) — Tyrosine Kinase Inhibitor