Abstract
Abstract CT016: Clinical and translational findings of pemigatinib in previously treated solid tumors with activating FGFR1-3 alterations in the FIGHT-207 study
Cancer research (Chicago, Ill.), Vol.83(8_Supplement), pp.CT016-CT016
04/14/2023
DOI: 10.1158/1538-7445.AM2023-CT016
Abstract
Abstract Background: Fibroblast growth factor receptor (FGFR) alterations are promising targets in different tumors. We report results of FIGHT-207, an open-label, single-arm phase 2 study of pemigatinib, a potent, selective FGFR1-3 inhibitor, in patients with previously treated unresectable or metastatic FGFR-altered solid tumors (NCT03822117). Methods: Patients were assigned to cohorts A (FGFR1-3 fusions), B (FGFR1-3 activating non-kinase domain mutations), and C (FGFR1-3 kinase domain mutations and alterations of unknown significance) and received continuous 13.5 mg pemigatinib once daily. Prior FGFR inhibitor treatment was prohibited. The primary endpoint was objective response rate (ORR) per RECIST v1.1 or RANO as confirmed by independent central review. Results: 107 patients were enrolled and assigned to cohorts A (n=49), B (n=32), and C (n=26). ORR in cohorts A, B, and C was 26.5%, 9.4%, and 3.8%, respectively. Responses were observed for multiple tumor types, including gliomas and gynecologic and pancreatic tumors (Table). Notably, we saw responses for several infrequent FGFR alterations, including an FGFR1 kinase domain mutation (K656E) and an FGFR2 extracellular in-frame deletion (FGFR2 I291_Y308Del). Among patients in cohorts A+B with centrally confirmed FGFR alterations, BAP1 co-alterations were observed in 47% (7/15) of responders, and TP53 co-alterations were present in 43% (23/53) of nonresponders. Safety was consistent with prior reports. Conclusions: In addition to cholangiocarcinoma, pemigatinib showed clinical activity in gliomas, gynecologic tumors, and pancreatic cancer and safety was consistent with prior reports. We observed responses in patients with previously unreported FGFR alterations, suggesting that a broader population of patients may benefit from FGFR inhibitors. Further correlative work to predict response to therapy is needed to better identify these patients. Table. Characteristics of Patients With Best Percentage Change From Baseline in Target Lesion Size ≥30% Patient Tumor Type FGFR alteration* BOR Best % Change From BL in Target Lesion Size PFS, mo Gliomas 1 Glioblastoma FGFR3 fusion CR −100.0 20.2† 2 Glioblastoma FGFR3 fusion PR −100.0 8.4† 3 Diffuse astrocytoma FGFR1 K656E mutation PR −80.7 8.0 Gynecologic 4 Cervical cancer FGFR3 fusion PR −100.0 6.4 5 Cervical cancer FGFR3 fusion PR −32.1 6.3 6 Endometrial cancer FGFR1 rearrangement SD −100.0 1.9† 7 Ovarian cancer FGFR2 fusion SD −44.0 2.1† 8 Cervical cancer FGFR2 C382R mutation SD −35.6 5.6 Pancreatic 9 Pancreatic adenocarcinoma FGFR2 fusion PR −72.1 8.4† 10 Pancreatic adenocarcinoma 2 FGFR2 fusions PR −54.9 8.9† 11 Pancreatic adenocarcinoma FGFR2 fusion PR −33.3 6.3† 12 Pancreatic adenocarcinoma FGFR2 fusion SD −100.0 2.7 Cholangiocarcinoma 13 Cholangiocarcinoma FGFR2 fusion PR −64.6 6.2 14 Cholangiocarcinoma FGFR2 fusion PR −61.4 9.9 15 Cholangiocarcinoma FGFR2 fusion PR −53.5 8.8 16 Cholangiocarcinoma FGFR2 C382R mutation PR −49.7 6.0 17 Cholangiocarcinoma FGFR2 fusion PR −46.2 5.9† 18 Cholangiocarcinoma FGFR2 fusion PR −43.2 10.5 19 Cholangiocarcinoma FGFR2 I291, Y308 deletion PR −42.5 14.8 20 Cholangiocarcinoma FGFR2 fusion PR −34.1 11.2† 21 Cholangiocarcinoma FGFR2 fusion SD −42.2 2.5† 22 Cholangiocarcinoma FGFR2 Y375C mutation SD −37.5 3.7† 23 Cholangiocarcinoma FGFR2 W290C mutation SD −34.0 10.5 Urothelial tract/bladder cancer 24 Urothelial tract/bladder cancer FGFR3 Y373C mutation PR −50.8 6.2† 25 Urothelial tract/bladder cancer FGFR3 Y373C mutation SD −30.0 3.9 Other 26 Non-small cell lung cancer FGFR2 fusion SD −72.0 4.1 27 Prostate cancer FGFR2 fusion SD −32.5 6.4 BL, baseline; BOR, best overall response; CR, complete response; FGFR, fibroblast growth factor receptor; PFS, progression-free survival; PR, partial response; SD, stable disease. * Includes FGFR alterations confirmed through both local and central genetic testing reports. † Censored. Citation Format: Jordi Rodon, Silvia Damian, Muhammad Furqan, Jesus Garcia-Donas, Hiroo Imai, Antoine Italiano, Iben Spanggaard, Makoto Ueno, Tomoya Yokota, Luisa Veronese, Natalia Oliveira, Xin Li, Aidan Gilmartin, Lipika Goyal. Clinical and translational findings of pemigatinib in previously treated solid tumors with activating FGFR1-3 alterations in the FIGHT-207 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT016.
Details
- Title: Subtitle
- Abstract CT016: Clinical and translational findings of pemigatinib in previously treated solid tumors with activating FGFR1-3 alterations in the FIGHT-207 study
- Creators
- Jordi Rodon - The University of Texas MD Anderson Cancer CenterSilvia Damian - Fondazione IRCCS Istituto Nazionale dei TumoriMuhammad Furqan - University of IowaJesus Garcia-Donas - Centro Oncológico de GaliciaHiroo Imai - Tohoku University HospitalAntoine Italiano - Institut BergoniéIben Spanggaard - Copenhagen University HospitalMakoto Ueno - Kanagawa Prefectural Hospital OrganizationTomoya Yokota - Shizuoka Cancer CenterLuisa Veronese - 10Incyte International Biosciences Sàrl, Morges, Switzerland;Natalia Oliveira - 10Incyte International Biosciences Sàrl, Morges, Switzerland;Xin Li - IncyteAidan Gilmartin - IncyteLipika Goyal - Harvard University
- Resource Type
- Abstract
- Publication Details
- Cancer research (Chicago, Ill.), Vol.83(8_Supplement), pp.CT016-CT016
- DOI
- 10.1158/1538-7445.AM2023-CT016
- ISSN
- 1538-7445
- eISSN
- 1538-7445
- Language
- English
- Date published
- 04/14/2023
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984410789802771
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