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Ref Type Journal Article
PMID (31446228)
Authors Morgensztern D, Karaseva N, Felip E, Delgado I, Burdaeva O, Dómine M, Lara P, Paik PK, Lassen U, Orlov S, Trigo J, Shomova M, Baker-Neblett K, Vasquez J, Wang X, Yan L, Mitrica I, DeYoung MP, Garrido P
Title An open-label phase IB study to evaluate GSK3052230 in combination with paclitaxel and carboplatin, or docetaxel, in FGFR1-amplified non-small cell lung cancer.
Journal Lung cancer (Amsterdam, Netherlands)
Vol 136
Issue
Date 2019 10
URL
Abstract Text GSK3052230 (FP-1039) is a soluble fusion protein that acts as ligand trap sequestering fibroblast growth factors (FGFs) involved in tumor growth and angiogenesis, while sparing the hormonal FGFs. Because of this selectivity, the molecule is predicted to avoid toxicities associated with small molecule inhibitors of FGFR, including hyperphosphatemia and retinal, nail, and skin toxicities. Herein we report the results of a phase 1b study where GSK3052330 was administered with standard of care chemotherapy in FGFR1-amplified squamous non-small cell lung cancer (sqNSCLC) patients.Eligible patients with stage IV or recurrent metastatic sqNSCLC harboring FGFR1 gene amplification received escalating doses of GSK3052230 in combination with paclitaxel and carboplatin at the starting doses 200 mg/m2 and AUC of 6, respectively, in the first line setting (Arm A) or docetaxel 75 mg/m2 in second line (Arm B). The primary endpoints of the study were safety and tolerability, to identify a maximum tolerated dose (MTD), and to assess overall response rate (ORR) based on investigator assessment.Twenty-nine patients were enrolled into the study, including 20 patients on Arm A and 9 patients on Arm B. There were no dose limiting toxicities in either Arm and the MTD was not reached. The most common adverse events (AEs) were compatible with the chemotherapy backbone used in each Arm, including neutropenia, alopecia, nausea, arthralgia, asthenia, diarrhea and peripheral neuropathy. The overall response rate and median progression-free survival were 47% and 5.5 months, respectively, for Arm A and 0% and 4.6 months, respectively, for Arm B.GSK3052230 is a novel FGFR pathway inhibitor, which is well tolerated in combination with chemotherapy. Importantly, AEs associated with small molecule inhibitors of FGFR were not observed, as predicted by the unique mechanism of action of this drug.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
GSK3052230 FP-1039|HGS1036|GSK-3052230|GSK 3052230 GSK3052230 (FP-1039) is an FGF ligand trap which prevents FGF1, FGF2, and FGF4 from binding corresponding receptors thereby preventing downstream signaling and activation (PMID: 26078430, PMID: 31065954, PMID: 31446228).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR1 amp lung squamous cell carcinoma predicted - sensitive Carboplatin + GSK3052230 + Paclitaxel Phase I Actionable In a Phase Ib trial, the combination therapy of GSK3052230 (FP-1039), Taxol (paclitaxel), and Paraplatin (carboplatin) demonstrated safety and was well-tolerable, and resulted in an overall response rate of 47% (9/19), with 9 patients achieving a partial response, and a progression-free survival of 5.5 months in patients with stage IV or recurrent metastatic squamous non-small cell lung cancer harboring FGFR1 amplification (PMID: 31446228; NCT01868022). 31446228