Reference Detail

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	Vol	Issue	Date	Pages	Journal Short Title
Lung cancer (Amsterdam, Netherlands)	136		2019 10	74-79	Lung Cancer

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
GSK3052230	GSK3052230	4	1

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