Infigratinib — Drug Monograph

Brand names: Truseltiq

Drug class: Tyrosine Kinase Inhibitor

Mechanism of Action

Oral, ATP-competitive, reversible pan-FGFR1-3 inhibitor. Blocks fibroblast growth factor receptor tyrosine kinase signaling, which is constitutively activated in tumors harboring FGFR2 fusions or rearrangements. As a reversible inhibitor, it is susceptible to secondary FGFR2 kinase-domain resistance mutations (e.g., the V565F gatekeeper mutation) — the resistance liability that covalent inhibitors such as futibatinib were designed to overcome.

FDA Indications

• Previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement (FDA accelerated approval May 2021; CBGJ398X2204: ORR ~23%, median DOR ~5 months). Note: voluntarily withdrawn from the US market in 2023 for business reasons — not due to a safety or efficacy signal.

Common Side Effects

• Hyperphosphatemia (on-target FGFR effect — near-universal)
• Nail toxicity (onycholysis, paronychia)
• Stomatitis
• Dry eye and dry mouth
• Fatigue
• Alopecia
• Palmar-plantar erythrodysesthesia
• Arthralgia

Clinical Pearl

Infigratinib was among the first FGFR inhibitors approved for FGFR2 fusion cholangiocarcinoma but was voluntarily withdrawn from the US market in 2023. As a reversible inhibitor it is vulnerable to acquired FGFR2 kinase-domain mutations (e.g., the V565F gatekeeper) — the same resistance mechanism the covalent inhibitor futibatinib retains activity against. Hyperphosphatemia is an on-target pharmacodynamic marker of FGFR inhibition, not merely an off-target toxicity.

Related Therapies & Mechanisms

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