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• W2764051792 abstract "Background: Fibroblast growth factor (FGF) signaling has a fundamental role in cancer development and tumor maintenance. FP-1039/GSK3052230 is a soluble decoy receptor that sequesters FGFs, including FGF2, blocking their ability to bind to and activate FGFRs, particularly FGFR1. This unique mechanism of action should avoid the on-target toxicities associated with small molecule pan FGFR kinase inhibitors, such as hyperphosphatemia and retinal, nail, and skin changes. MPM remains a disease with poor prognosis and few effective therapies, and preclinical models of MPM are particularly sensitive to inhibition of FGF/FGFR signaling by FP-1039/GSK3052230. Methods: Herein, the analysis of patients with untreated, unresectable MPM is reported. The MPM arm of the study evaluated the safety and efficacy of FP-1039/GSK3052230 (IV weekly) in combination with standard pemetrexed+cisplatin. The study design involved dose escalation until MTD followed by a cohort expansion phase. Endpoints included safety, overall response rate by modified RECIST 1.1, disease control rate (DCR), PFS, and exploratory translational objectives. Results: As of the cutoff date of 17 Mar 2017, 36 patients were dosed at 10, 15 and 20 mg/kg doses of FP-1039/GSK3052230. Three DLTs were observed at 20 mg/kg but none occurred at 15 mg/kg; therefore, MTD was declared at this dose. Most common related adverse events (all grades) were: nausea (56%) decreased appetite (36%), fatigue (33%), and infusion reaction (33%). The confirmed objective response rate (ORR) of all evaluable patients at or below the MTD was 48% (13/27 PRs), with disease control rate (DCR) of 100%. The median PFS was 7.4 months. As of 8 May 2017, six patients stayed on the study for over 1 year, of which 3 were still ongoing. Results of exploratory biomarker analyses will also be presented. Conclusions: The MTD of FP-1039/GSK3052230 (15 mg/kg) in combination with pemetrexed+cisplatin in MPM was well tolerated, and durable responses were observed. Importantly, AEs associated with small-molecule pan FGFR kinase inhibitors were not observed, as predicted by the unique mechanism of action of this drug. Study sponsored by GSK; clinical trial information: NCT01868022. Clinical trial identification: NCT01868022 Legal entity responsible for the study: GlaxoSmithKline Funding: GlaxoSmithKline Disclosure: D.A. Fennell: Advisory Board/consultant – Astra Zeneca, BMS, Bayer, Boehringer Ingelheim, Clovis, Roche, Eli Lilly, MSD H.L. Kindler: Advisor: Aduro; AZ; Bayer; Celgene; Genentech/Roche; Gilead; GSK; MedImmune; Merck; Plexxikon; Verastem. Grants: AB Science; Aduro; Astellas Pharma; AZ; Bayer; Celgene; GSK; Incyte; MedImmune; Merck; Verastem. Expert Testimony: Aduro S. Viteri: Grants: AbbVie, ARIAD, Astex, AZ, BI, Clovis, CytRx, Daiichi Sankyo, GSK, Hanmi, Incyte, Merck KGaA, Novartis, Pfizer, Puma, Roche, Servier, Vaxon. Advisor: BI, Clovis, Idea Pharma, Novartis, Promega Biotech Ibérica, Roche, Targovax S. Gadgeel: Advisor/Board member: Genentech/Roche, Pfizer, Ariad, Astra-Zeneca Speakers bureau: Genetech/Roche, Astra-Zeneca Travel Compensation: Genentech/Roche P. Garrido Lopez: Advisor/Board member: MSD, Pfizer, BMS, Novartis, Roche, BI, Guardant Speakers bureau: MSD, Pfizer, BMS, Novartis, Roche Honorarium recipient: BI D. Morgensztern: Advisor/Board member: Abbvie, Celgene, Bristo-Myers Squibb J.F. Vansteenkiste: Grants/research support recipient: AZ Honorarium/consulting: AZ, Novartis, MSD, BI, Eli-Lilly, Roche X. Wang: Full-time employee with GlaxoSmithkline A. Sharabidze: Consultant at GSK M.P. Deyoung: Full time employee and stock owner of GSK K.P. Baker: Full time employee of Five Prime Therapeutics L. Yan, I. Mitrica: Full time employee of GSK and stock owner All other authors have declared no conflicts of interest." @default.
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• W2764051792 date "2017-09-01" @default.
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• W2764051792 title "Multicenter, nonrandomized, open-label Phase 1b study of FP-1039/GSK3052230 with chemotherapy: results in malignant pleural mesothelioma (MPM)" @default.
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