Pemigatinib For Previously Treated Central Nervous System Tumors With Activating FGFR Mutations or Translocations: Results From FIGHT-207
Iben Spanggaard1, Marc Matrana2, Caio Rocha-Lima3, Amit Mahipal4, Maria Vieito5, Alice Hervieu6, Myung-Ju Ahn7, Lipika Goyal8, Jordi Rodon Ahnert9, Luisa Veronese10, Natalia Oliveira10, Xin Li11, Michael Schaffer11, Santosh Kesari12
1Rigshospitalet Copenhagen University Hospital, 2Ochsner Cancer Institute, Ochsner Clinic Foundation, 3Wake Forest University School of Medicine, 4Mayo Clinic; Seidman Cancer Center/Case Western Reserve University, 5Vall d'Hebron University Hospital, 6Centre Georges-François Leclerc, 7Samsung Medical Center, 8Mass General Cancer Center, Harvard Medical School, 9The University of Texas MD Anderson Cancer Center, 10Incyte International Biosciences Sàrl, 11Incyte Corporation, 12Providence Southern California Research Clinical Institute, Saint John’s Cancer Institute, Pacific Neuroscience Institute
Objective:
To report the activity of pemigatinib in the subset of FIGHT-207 patients with previously treated CNS tumors.
Background:
Dysregulated fibroblast growth factor receptor (FGFR) signaling impacts glioma progression. Pemigatinib is a potent, selective FGFR1–3 inhibitor with antitumor activity in solid tumors. The open-label, single-arm phase 2 FIGHT-207 study evaluated pemigatinib in previously treated advanced/metastatic or surgically unresectable solid tumors with activating FGFR mutations/translocations, including CNS tumors (NCT03822117).
Design/Methods:
Eligible patients were adults with advanced/metastatic or surgically unresectable solid tumors that progressed after ≥1 prior therapy. Patients were assigned into cohorts based on confirmed FGFR status (FGFR1–3 fusions/rearrangements, mutations, and other molecular alterations). Patients received 13.5 mg pemigatinib QD (continuous dosing) until disease progression or unacceptable toxicity. Primary endpoints were objective response rates per RECIST v1.1 or RANO assessed by independent central review. Secondary endpoints included the rate of treatment-emergent adverse events (TEAEs).
Results:
CNS tumors were GBM (n=9), low-grade pediatric-type glioma (n=1), grade II infiltrating glioma (n=1), grade II diffuse astrocytoma (n=1), and polymorphous low-grade neuroepithelial tumor of the young (n=1). FGFR alterations were FGFR3-TACC3 fusions (n=9 [2 unconfirmed], 69.2%), FGFR1 K656E mutations (n=2, 15.4%), unconfirmed FGFR1 N546K mutation (n=1, 7.7%), and FGFR1-MITF fusion (n=1, 7.7%). Ten (76.9%) patients each received previous radiation and surgery; 11 (84.6%) received prior systemic therapy. One (FGFR3-TACC3 fusion) and 2 patients (FGFR3-TACC3 fusion, n=1; FGFR1 K656E, n=1) achieved complete and partial responses, respectively. Stable and progressive disease was observed in 3 (FGFR3-TACC3 fusion, n=2; FGFR1 N546K, n=1) and 6 patients (FGFR3-TACC3 fusion, n=4; FGFR1 NK656E, n=1; FGFR1-MITF fusion, n=1), respectively; 1 patient was not evaluable. TEAE incidence was similar to the previously reported safety profile.
Conclusions:
Pemigatinib showed promising activity in patients with CNS tumors with activating FGFR1–3 fusions/rearrangements; no new TEAEs were observed. The ongoing FIGHT-209 study will provide additional data in this population.