PMID- 31446228 OWN - NLM STAT- MEDLINE DCOM- 20200721 LR - 20201010 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 136 DP - 2019 Oct TI - 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. PG - 74-79 LID - S0169-5002(19)30611-7 [pii] LID - 10.1016/j.lungcan.2019.08.011 [doi] 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/m(2) and AUC of 6, respectively, in the first line setting (Arm A) or docetaxel 75 mg/m(2) 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. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Morgensztern, Daniel AU - Morgensztern D AD - Washington University School of Medicine, St. Louis, MO, USA. FAU - Karaseva, Nina AU - Karaseva N AD - St. Petersburg City Oncology Dispensary, St. Petersburg, Russian Federation. FAU - Felip, Enriqueta AU - Felip E AD - Servicio de Oncologia, Hospital General Universitario Vall d'Hebron, Barcelona, Spain. FAU - Delgado, Ignacio AU - Delgado I AD - Hospital Infanta Cristina, Badajoz, Spain. FAU - Burdaeva, Olga AU - Burdaeva O AD - Arkhangelsk Regional Oncology Dispensary, Arkhangelsk, Russian Federation. FAU - Domine, Manuel AU - Domine M AD - Fundacion Jimenez Diaz, Madrid, Spain. FAU - Lara, Primo AU - Lara P AD - University of California, Davis Medical Center, Sacramento, CA, USA. FAU - Paik, Paul K AU - Paik PK AD - Memorial Sloan Kettering Cancer Center, New York, NY, USA. FAU - Lassen, Ulrik AU - Lassen U AD - Department of Oncology Rigshospitalet, Copenhagen, Denmark. FAU - Orlov, Sergey AU - Orlov S AD - First Pavlov State Medical University, St. Petersburg, Russian Federation. FAU - Trigo, Jose AU - Trigo J AD - Hospital Universitario Virgen de la Victoria, Malaga, Spain. FAU - Shomova, Marina AU - Shomova M AD - Regional Clinical Oncology Dispensary, Ryazan, Russian Federation. FAU - Baker-Neblett, Katherine AU - Baker-Neblett K AD - GlaxoSmithKline, Inc., Collegeville, PA, USA. FAU - Vasquez, James AU - Vasquez J AD - GlaxoSmithKline, Inc., Collegeville, PA, USA. FAU - Wang, Xiaowei AU - Wang X AD - GlaxoSmithKline, Inc., Collegeville, PA, USA. FAU - Yan, Li AU - Yan L AD - GlaxoSmithKline, Inc., Collegeville, PA, USA. FAU - Mitrica, Ionel AU - Mitrica I AD - GlaxoSmithKline, Inc., Collegeville, PA, USA. FAU - DeYoung, M Phillip AU - DeYoung MP AD - GlaxoSmithKline, Inc., Collegeville, PA, USA. Electronic address: maurice.p.deyoung@gsk.com. FAU - Garrido, Pilar AU - Garrido P AD - Medical Oncology Department, Hospital Universitario Ramon y Cajal, Madrid, Spain. Electronic address: pilargarridol@gmail.com. LA - eng PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190814 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 15H5577CQD (Docetaxel) RN - BG3F62OND5 (Carboplatin) RN - EC 2.7.10.1 (FGFR1 protein, human) RN - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Carboplatin/administration & dosage/pharmacokinetics MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/*genetics/pathology MH - Combined Modality Therapy MH - Docetaxel/administration & dosage/pharmacokinetics MH - Female MH - *Gene Amplification MH - Humans MH - Lung Neoplasms/*drug therapy/*genetics/pathology MH - Male MH - Middle Aged MH - Paclitaxel/administration & dosage/pharmacokinetics MH - Receptor, Fibroblast Growth Factor, Type 1/*genetics MH - Retreatment MH - Treatment Outcome OTO - NOTNLM OT - Combination therapy OT - FGFR1 OT - Ligand trap OT - Phase 1 OT - Squamous non-small cell lung cancer EDAT- 2019/08/26 06:00 MHDA- 2020/07/22 06:00 CRDT- 2019/08/26 06:00 PHST- 2019/05/21 00:00 [received] PHST- 2019/07/11 00:00 [revised] PHST- 2019/08/13 00:00 [accepted] PHST- 2019/08/26 06:00 [pubmed] PHST- 2020/07/22 06:00 [medline] PHST- 2019/08/26 06:00 [entrez] AID - S0169-5002(19)30611-7 [pii] AID - 10.1016/j.lungcan.2019.08.011 [doi] PST - ppublish SO - Lung Cancer. 2019 Oct;136:74-79. doi: 10.1016/j.lungcan.2019.08.011. Epub 2019 Aug 14.