A dysregulation of fibroblast growth factor receptor (FGFR) signaling, resulting from somatic FGFR alterations (activating mutations, amplifications, and fusions or rearrangements), has been implicated in a wide range of tumor types; now a new first-in-human study recently published on Annals of Oncology shows that targeting FGFR 1-3 with the selective inhibitor pemigatinib is safe. The drug has also demonstrated pharmacological and clinical activity.
The phase I/II FIGHT-101 study evaluated safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of pemigatinib as monotherapy or in combination therapy for refractory advanced malignancies, with and without FGF and FGFR gene alterations. The trial enrolled 128 patients treated with pemigatinib once daily intermittently (2 weeks on/1 week off) or continuously; no dose-limiting toxicities were reported and doses > 4 mg were pharmacologically active. Overall, 12 partial responses were achieved, most commonly in cholangiocarcinoma; median duration of response was 7.3 months and overall response rate was highest for patients with FGFR fusions/rearrangements, followed by those with FGFR mutations.
Results, obtained in patients treated with pemigatinib monotherapy, showed a manageable safety profile and pharmacodynamic and clinical activity for pemigatinib, with responses seen across tumors and driven by FGFR fusions/rearrangements and mutations: authors, underlining the benefit of precision therapy even in early phase trials, suggest a registrational study in cholangiocarcinoma and phase II/III trials in multiple tumor types.