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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

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Harvard

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 2019, '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' Lung cancer, vol. 136, pp. 74-79. https://doi.org/10.1016/j.lungcan.2019.08.011

APA

CBE

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. 2019. 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. Lung cancer. 136:74-79. https://doi.org/10.1016/j.lungcan.2019.08.011

MLA

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Author

Morgensztern, Daniel ; Karaseva, Nina ; Felip, Enriqueta ; Delgado, Ignacio ; Burdaeva, Olga ; Dómine, Manuel ; Lara, Primo ; Paik, Paul K ; Lassen, Ulrik ; Orlov, Sergey ; Trigo, José ; Shomova, Marina ; Baker-Neblett, Katherine ; Vasquez, James ; Wang, Xiaowei ; Yan, Li ; Mitrica, Ionel ; DeYoung, M Phillip ; Garrido, Pilar. / 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. In: Lung cancer. 2019 ; Vol. 136. pp. 74-79.

Bibtex

@article{789001c2c6204d23a5c12e36bb26a81a,
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",
abstract = "OBJECTIVES: 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.METHODS AND METHODS: 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.RESULTS: 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.CONCLUSION: 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.",
author = "Daniel Morgensztern and Nina Karaseva and Enriqueta Felip and Ignacio Delgado and Olga Burdaeva and Manuel D{\'o}mine and Primo Lara and Paik, {Paul K} and Ulrik Lassen and Sergey Orlov and Jos{\'e} Trigo and Marina Shomova and Katherine Baker-Neblett and James Vasquez and Xiaowei Wang and Li Yan and Ionel Mitrica and DeYoung, {M Phillip} and Pilar Garrido",
note = "Copyright {\circledC} 2019 Elsevier B.V. All rights reserved.",
year = "2019",
month = "10",
doi = "10.1016/j.lungcan.2019.08.011",
language = "English",
volume = "136",
pages = "74--79",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",

}

RIS

TY - JOUR

T1 - 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

AU - Morgensztern, Daniel

AU - Karaseva, Nina

AU - Felip, Enriqueta

AU - Delgado, Ignacio

AU - Burdaeva, Olga

AU - Dómine, Manuel

AU - Lara, Primo

AU - Paik, Paul K

AU - Lassen, Ulrik

AU - Orlov, Sergey

AU - Trigo, José

AU - Shomova, Marina

AU - Baker-Neblett, Katherine

AU - Vasquez, James

AU - Wang, Xiaowei

AU - Yan, Li

AU - Mitrica, Ionel

AU - DeYoung, M Phillip

AU - Garrido, Pilar

N1 - Copyright © 2019 Elsevier B.V. All rights reserved.

PY - 2019/10

Y1 - 2019/10

N2 - OBJECTIVES: 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.METHODS AND METHODS: 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.RESULTS: 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.CONCLUSION: 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.

AB - OBJECTIVES: 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.METHODS AND METHODS: 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.RESULTS: 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.CONCLUSION: 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.

U2 - 10.1016/j.lungcan.2019.08.011

DO - 10.1016/j.lungcan.2019.08.011

M3 - Journal article

VL - 136

SP - 74

EP - 79

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

ER -

ID: 58970617