Journal article
Pemigatinib in previously treated solid tumors with activating FGFR1-FGFR3 alterations: phase 2 FIGHT-207 basket trial
Nature medicine, Vol.30(6), pp.1645-1654
05/06/2024
DOI: 10.1038/s41591-024-02934-7
PMCID: PMC11186762
PMID: 38710951
Abstract
Fibroblast growth factor receptor (FGFR) alterations drive oncogenesis in multiple tumor types. Here we studied pemigatinib, a selective, potent, oral FGFR1-FGFR3 inhibitor, in the phase 2 FIGHT-207 basket study of FGFR-altered advanced solid tumors. Primary end points were objective response rate (ORR) in cohorts A (fusions/rearrangements) and B (activating non-kinase domain mutations). Secondary end points were progression-free survival, duration of response and overall survival in cohorts A and B, and safety. Exploratory end points included ORR of cohort C (kinase domain mutations, potentially pathogenic variants of unknown significance) and analysis of co-alterations associated with resistance and response. ORRs for cohorts A, B and C were 26.5%, 9.4% and 3.8%, respectively. Tumors with no approved FGFR inhibitors or those with alterations not previously confirmed to be sensitive to FGFR inhibition had objective responses. In cohorts A and B, the median progression-free survival was 4.5 and 3.7 months, median duration of response was 7.8 and 6.9 months and median overall survival was 17.5 and 11.4 months, respectively. Safety was consistent with previous reports. The most common any-grade treatment-emergent adverse events were hyperphosphatemia (84%) and stomatitis (53%). TP53 co-mutations were associated with lack of response and BAP1 alterations with higher response rates. FGFR1-FGFR3 gatekeeper and molecular brake mutations led to acquired resistance. New therapeutic areas for FGFR inhibition and drug failure mechanisms were identified across tumor types. ClinicalTrials.gov identifier: NCT03822117 .
Details
- Title: Subtitle
- Pemigatinib in previously treated solid tumors with activating FGFR1-FGFR3 alterations: phase 2 FIGHT-207 basket trial
- Creators
- Jordi Rodón - The University of Texas MD Anderson Cancer CenterSilvia Damian - Fondazione IRCCS Istituto Nazionale dei TumoriMuhammad Furqan - University of IowaJesús García-Donas - Centro Oncológico de GaliciaHiroo Imai - Tohoku University HospitalAntoine Italiano - Institut BergoniéIben Spanggaard - Copenhagen University HospitalMakoto Ueno - Kanagawa Prefectural Hospital OrganizationTomoya Yokota - Shizuoka Cancer CenterMaria Luisa Veronese - IncyteNatalia Oliveira - IncyteXin Li - IncyteAidan Gilmartin - IncyteMichael Schaffer - IncyteLipika Goyal - Harvard University
- Resource Type
- Journal article
- Publication Details
- Nature medicine, Vol.30(6), pp.1645-1654
- DOI
- 10.1038/s41591-024-02934-7
- PMID
- 38710951
- PMCID
- PMC11186762
- eISSN
- 1546-170X
- Language
- English
- Electronic publication date
- 05/06/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984623027802771
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