FIGHT-101, a first-in-human study of potent and selective FGFR 1-3 inhibitor pemigatinib in pan-cancer patients with FGF/FGFR alterations and advanced malignancies

Ann Oncol. 2022 May;33(5):522-533. doi: 10.1016/j.annonc.2022.02.001. Epub 2022 Feb 14.


Background: The phase I/II FIGHT-101 study (NCT02393248) evaluated safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of pemigatinib, a potent and selective fibroblast growth factor receptor (FGFR) 1-3 inhibitor, as monotherapy or in combination therapy, for refractory advanced malignancies, with and without fibroblast growth factor (FGF) and receptor (FGFR) gene alterations.

Patients and methods: Eligible, molecularly unselected patients with advanced malignancies were included in part 1 (dose escalation; 3 + 3 design) to determine the maximum tolerated dose. Part 2 (dose expansion) evaluated the recommended phase II dose in tumors with or where FGF/FGFR activity is relevant.

Results: Patients (N = 128) received pemigatinib 1-20 mg once daily intermittently (2 weeks on/1 week off; n = 70) or continuously (n = 58). No dose-limiting toxicities were reported. Doses ≥4 mg were pharmacologically active (maximum tolerated dose not reached; recommended phase II dose 13.5 mg once daily). The most common treatment-emergent adverse event (TEAE) was hyperphosphatemia (75.0%; grade ≥3, 2.3%); the most common grade ≥3 TEAE was fatigue (10.2%). Dose interruption, dose reduction, and TEAE-related treatment discontinuation occurred in 66 (51.6%), 14 (10.9%), and 13 (10.2%) patients, respectively. Overall, 12 partial responses were achieved, most commonly in cholangiocarcinoma (n = 5) as well as in a broad spectrum of tumors including head and neck, pancreatic, gallbladder, uterine, urothelial carcinoma, recurrent pilocytic astrocytoma, and non-small-cell lung cancer (each n = 1); median duration of response was 7.3 months [95% confidence interval (CI) 3.3-14.5 months]. Overall response rate was highest for patients with FGFR fusions/rearrangements [n = 5; 25.0% (95% CI 8.7% to 49.1%)], followed by those with FGFR mutations [n = 3; 23.1% (95% CI 5.0% to 53.8%)].

Conclusions: Pemigatinib was associated with a manageable safety profile and pharmacodynamic and clinical activity, with responses seen across tumors and driven by FGFR fusions/rearrangements and mutations. These results prompted a registrational study in cholangiocarcinoma and phase II/III trials in multiple tumor types demonstrating the benefit of precision therapy, even in early phase trials.

Keywords: FGFR; advanced malignancies; genomic profiling; pemigatinib; phase I/II clinical trial.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Bile Duct Neoplasms* / drug therapy
  • Bile Ducts, Intrahepatic / pathology
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Transitional Cell* / drug therapy
  • Cholangiocarcinoma* / drug therapy
  • Cholangiocarcinoma* / genetics
  • Female
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / therapeutic use
  • Humans
  • Lung Neoplasms* / drug therapy
  • Male
  • Morpholines
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasms* / chemically induced
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines
  • Pyrroles
  • Receptors, Fibroblast Growth Factor / genetics
  • Urinary Bladder Neoplasms* / drug therapy


  • Morpholines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrroles
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factors
  • pemigatinib

Associated data