A phase Ib study of GSK3052230, an FGF ligand trap in combination with pemetrexed and cisplatin in patients with malignant pleural mesothelioma

Abstract

is an employee of MSKCC and MSKCC has an institutional collaboration agreement with IBM for Watson for Oncology and receives royalties from IBM, is the Chair of the Board of Directors of the Mesothelioma Applied Research Foundation, reports receiving commercial research grants from MedImmune, Epizyme, Polaris, Sellas Life Sciences, BMS, and Millenium, and is a consultant/advisory board member for Epizyme and Aldeyra Therapeutics. J.F. Vansteenkiste reports receiving research funding/honoraria from MSD, AZ, BMS, BI, and Roche and is a consultant/advisory board member for AZ, BMS, BI, MSD, and Roche. K. Baker-Neblett, X. Wang, L. Yan, I. Mitrica, and M.P. DeYoung are employees of and hold ownership interest in GlaxoSmithKline. J. Vasquez is an employee of GlaxoSmithKline. D.I. Bellovin is an employee of and holds ownership interest in Five Prime Therapeutics. J.H.M. Schellens is an employee of and holds ownership interest in Modra Pharmaceuticals and is a consultant/advisory board member for Debiopharm. J.M. Trigo reports receiving speakers' bureau honoraria from BMS and BI and is a consultant/advisory board member for BMS, BI, Merck, and Takeda. No potential conflicts of interest were disclosed by the other authors. Ethical approvalAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Fibroblast growth factor receptors in cancer: genetic alterations, diagnostics, therapeutic targets and mechanisms of resistance

“… 80 Further studies combining FP-1039 with pemetrexed and cisplatin in mesothelioma patients and with paclitaxel and carboplatin in patients with FGFR1 -amplified non-small cell lung cancer have also been completed. 81 , 82 …”

Expression of FGFR1–4 in Malignant Pleural Mesothelioma Tissue and Corresponding Cell Lines and its Relationship to Patient Survival and FGFR Inhibitor Sensitivity

“…Marek et al found a link between high FGFR1 protein expression determined by immunoblotting in MPM cell lines and sensitivity to the FGFR inhibitors ponatinib and FP1039/GSK3052230 [10]. The latter inhibitor was recently tested in a phase Ib study in MPM [38]. Quispel-Janssen et al reported that loss of BAP1 was linked to increased FGFR inhibitor sensitivity and elevated FGFR/FGF expression in MPM cells [15].…”

Use of preclinical models for malignant pleural mesothelioma

“… 79 High-throughput drug sensitivity testing of a panel of commercial and primary early passage mesothelioma cell lines identified a subgroup of MPM lines highly sensitive to FGFR inhibition as well as death receptor agonist tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), associated with BAP1 loss. 80 81 A phase Ib clinical trial of a FGF ligand trap in combination with pemetrexed/cisplatin chemotherapy appeared to show durable responses, 82 but further validation is required before loss of BAP1 can be used as a biomarker for responsiveness to FGF/FGFR inhibitors or TRAIL.…”