A Phase 2 Study of Pemigatinib (FIGHT-203; INCB054828) in Patients with Myeloid/Lymphoid Neoplasms (MLNs) with Fibroblast Growth Factor Receptor 1 (FGFR1) Rearrangement (MLN FGFR1)

▪ Background: MLN FGFR1 comprise rare hematologic neoplasms belonging to the World Health Organization major category of fusion tyrosine kinases typically associated with eosinophilia. MLN FGFR1 may present with chronic or blast phase (CP or BP) involvement of bone marrow (BM) and/or BP involvement of extramedullary disease (EMD) sites. Diagnosis requires t(8;13)(p11;q12) or another translocation involving chromosome band 8p11 that results in constitutive activation of FGFR1. Hydroxyurea, multikinase inhibitors with anti-FGFR1 activity (eg, midostaurin, ponatinib), or intensive multi-agent chemotherapy often lead to partial (PR) or short-lived complete responses (CR); complete cytogenetic responses (CCyRs) are rare. Given the poor prognosis of MLN FGFR1 and the potential for transformation to BP, a primary goal is to achieve deep responses to bridge patients (pts) to allogeneic hematopoietic stem cell transplant (HSCT). Pemigatinib is a selective and potent inhibitor of FGFR1-3 approved in the US, EU, and Japan for the treatment of adults with previously treated, unresectable, locally advanced, or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement. This is an analysis of data from the ongoing FIGHT-203 study of pemigatinib in adults with MLN FGFR1 (NCT03011372). Methods: FIGHT-203 is a phase 2, multicenter trial enrolling pts ≥18 years of age with MLN FGFR1. Initially, pts had to have received ≥1 prior therapy; the starting dosing was pemigatinib 13.5 mg daily (2 wks; 1 wk off). With amendments, pts without prior therapy were also eligible and the starting dose was changed to 13.5 mg daily on a continuous schedule. The primary endpoint is CR rate; secondary endpoints include rates of overall response (ORR [CR + PR]), CCyR or partial CyR (PCyR), and safety. All primary and secondary endpoints were investigator-assessed according to protocol-defined criteria including modified response criteria for MDS/MPN and modified Lugano criteria for EMD. CCyR and PCyR were defined as 100% or ≥50% reduction in 8p11-rearranged metaphases or cells, respectively, on karyotyping or fluorescence in situ hybridization. Responses were also adjudicated retrospectively by a Central Review Committee (CRC) with CRC-defined criteria based on local lab and radiologic results and central histopathology review; local and central (given priority) cytogenetic results were used by the CRC. Results: At data cutoff (Dec 31, 2020), 34 pts were enrolled and treated (sa