RT Journal Article
T1 A phase Ib study of GSK3052230, an FGF ligand trap in combination with pemetrexed and cisplatin in patients with malignant pleural mesothelioma.
A1 van Brummelen, Emilie M J
A1 Levchenko, Evgeny
A1 Dómine, Manuel
A1 Fennell, Dean A
A1 Kindler, Hedy L
A1 Viteri, Santiago
A1 Gadgeel, Shirish
A1 López, Pilar Garrido
A1 Kostorov, Vladimir
A1 Morgensztern, Daniel
A1 Orlov, Sergey
A1 Zauderer, Marjorie G
A1 Vansteenkiste, Johan F
A1 Baker-Neblett, Katherine
A1 Vasquez, James
A1 Wang, Xiaowei
A1 Bellovin, David I
A1 Schellens, Jan H M
A1 Yan, Li
A1 Mitrica, Ionel
A1 DeYoung, M Phillip
A1 Trigo, Jose
K1 Combination therapy
K1 FGF
K1 Ligand trap
K1 Mesothelioma
K1 Phase 1
AB Background Fibroblast growth factors (FGFs) have a fundamental role in cancer. Sequestering FGFs with GSK3052230 (FP-1039) blocks their ability to activate FGFRs while avoiding toxicities associated with small molecule inhibitors of FGFR, including hyperphosphatemia and retinal, nail, and skin toxicities. Methods A multicenter, open-label, phase Ib study evaluated weekly GSK3052230 added to pemetrexed/cisplatin in patients with treatment-naive, unresectable malignant pleural mesothelioma. Doses were escalated according to a 3 + 3 design, followed by cohort expansion at the maximum tolerated dose (MTD). Endpoints included safety, overall response rate, progression-free survival, and pharmacokinetics. Results 36 patients were dosed at 10, 15, and 20 mg/kg doses of GSK3052230. Three dose-limiting toxicities were observed at 20 mg/kg and one at 15 mg/kg. The MTD was defined as 15 mg/kg and used for cohort expansion. The most common treatment-related adverse events (AEs) were nausea (56%), decreased appetite (36%), infusion reactions (36%), decreased neutrophil counts (36%), and fatigue (33%). The confirmed ORR was 39% (95% CI: 23.1-56.5) (14/36 PRs) and 47% had stable disease (17/36), giving a disease control rate of 86%. At 15 mg/kg GSK3052230 (n = 25), the ORR was 44% (95% CI: 24.4-65.1), and the median PFS was 7.4 months (95% CI: 6.7-13.4). Four patients had disease control for over 1 year, and three were still ongoing. Conclusion At 15 mg/kg weekly, GSK3052230 was well tolerated in combination with pemetrexed/cisplatin and durable responses were observed. Importantly, AEs associated with small molecule inhibitors of FGFR were not observed, as predicted by the unique mechanism of action of this drug.
PB Springer Nature
YR 2019
FD 2019-05-07
LK http://hdl.handle.net/10668/13925
UL http://hdl.handle.net/10668/13925
LA en
NO van Brummelen EMJ, Levchenko E, Dómine M, Fennell DA, Kindler HL, Viteri S, et al. A phase Ib study of GSK3052230, an FGF ligand trap in combination with pemetrexed and cisplatin in patients with malignant pleural mesothelioma. Invest New Drugs. 2020 Apr;38(2):457-467
DS RISalud
RD Apr 7, 2025