Universität zu Köln

Nogova, Lucia, Sequist, Lecia V., Garcia, Jose Manuel Perez, Andre, Fabrice, Delord, Jean-Pierre, Hidalgo, Manuel, Schellens, Jan H. M., Cassier, Philippe A., Camidge, D. Ross, Schuler, Martin, Vaishampayan, Ulka ORCID: 0000-0001-5800-4571, Burris, Howard, Tian, G. Gary, Campone, Mario, Wainberg, Zev A., Lim, Wan-Teck ORCID: 0000-0002-4655-0206, LoRusso, Patricia, Shapiro, Geoffrey I., Parker, Katie, Chen, Xueying, Choudhury, Somesh, Ringeisen, Francois, Graus-Porta, Diana, Porter, Dale, Isaacs, Randi, Buettner, Reinhard and Wolf, Juergen (2017). Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study. J. Clin. Oncol., 35 (2). S. 157 - 176. ALEXANDRIA: AMER SOC CLINICAL ONCOLOGY. ISSN 1527-7755

Full text not available from this repository.

Abstract

Purpose This two-part, first-in-human study was initiated in patientswith advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors (FGFRs) to determine the maximum tolerated dose (MTD), the recommended phase II dose (RP2D), and the schedule, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of oral BGJ398, a selective FGFR1-3 tyrosine kinase inhibitor. Patients and Methods Adult patients were treated with escalating dosages of BGJ398 5 to 150 mg once daily or 50 mg twice daily continuously in 28-day cycles. During expansion at the MTD, patients with FGFR1amplified squamous cell non-small-cell lung cancer (sqNSCLC; arm 1) or other solid tumors with FGFR genetic alterations (mutations/amplifications/fusions) received BGJ398 daily on a continuous schedule (arm 2), or on a 3-weeks-on/1-week-off schedule (arm 3). Results Data in 132 patients from the escalation and expansion arms are reported (May 15, 2015, cutoff). The MTD, 125 mg daily, was determined on the basis of dose-limiting toxicities in four patients (100 mg, grade 3 aminotransferase elevations [n = 1]; 125 mg, hyperphosphatemia [n = 1]; 150 mg, grade 1 corneal toxicity [n = 1] and grade 3 aminotransferase elevations [n = 1]). Common adverse events in patients treated at the MTD (n = 57) included hyperphosphatemia (82.5%), constipation (50.9%), decreased appetite (45.6%), and stomatitis (45.6%). A similar safety profile was observed using the 3-weeks-on/1-week-off schedule (RP2D). However, adverse event-related dose adjustments/ interruptions were less frequent with the 3-weeks-on/1-week-off (50.0%) versus the continuous (73.7%) schedule. Antitumor activity (seven partial responses [six confirmed]) was demonstrated with BGJ398 doses $ 100 mg in patients with FGFR1-amplified sqNSCLC and FGFR3-mutant bladder/urothelial cancer. Conclusion BGJ398 at the MTD/RP2D had a tolerable and manageable safety profile and showed antitumor activity in several tumor types, including FGFR1-amplified sqNSCLC and FGFR3-mutant bladder/ urothelial cancers. (C) 2016 by American Society of Clinical Oncology

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nogova, Lucia UNSPECIFIED UNSPECIFIED UNSPECIFIED Sequist, Lecia V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Garcia, Jose Manuel Perez UNSPECIFIED UNSPECIFIED UNSPECIFIED Andre, Fabrice UNSPECIFIED UNSPECIFIED UNSPECIFIED Delord, Jean-Pierre UNSPECIFIED UNSPECIFIED UNSPECIFIED Hidalgo, Manuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Schellens, Jan H. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cassier, Philippe A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Camidge, D. Ross UNSPECIFIED UNSPECIFIED UNSPECIFIED Schuler, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Vaishampayan, Ulka UNSPECIFIED orcid.org/0000-0001-5800-4571 UNSPECIFIED Burris, Howard UNSPECIFIED UNSPECIFIED UNSPECIFIED Tian, G. Gary UNSPECIFIED UNSPECIFIED UNSPECIFIED Campone, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Wainberg, Zev A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lim, Wan-Teck UNSPECIFIED orcid.org/0000-0002-4655-0206 UNSPECIFIED LoRusso, Patricia UNSPECIFIED UNSPECIFIED UNSPECIFIED Shapiro, Geoffrey I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Parker, Katie UNSPECIFIED UNSPECIFIED UNSPECIFIED Chen, Xueying UNSPECIFIED UNSPECIFIED UNSPECIFIED Choudhury, Somesh UNSPECIFIED UNSPECIFIED UNSPECIFIED Ringeisen, Francois UNSPECIFIED UNSPECIFIED UNSPECIFIED Graus-Porta, Diana UNSPECIFIED UNSPECIFIED UNSPECIFIED Porter, Dale UNSPECIFIED UNSPECIFIED UNSPECIFIED Isaacs, Randi UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-242643
DOI:	10.1200/JCO.2016.67.2048
Journal or Publication Title:	J. Clin. Oncol.
Volume:	35
Number:	2
Page Range:	S. 157 - 176
Date:	2017
Publisher:	AMER SOC CLINICAL ONCOLOGY
Place of Publication:	ALEXANDRIA
ISSN:	1527-7755
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROTEIN EXPRESSION; FGFR1; CARCINOMA; SENSITIVITY; NVP-BGJ398; MUTATIONS; DOCETAXEL; NIVOLUMAB; DRIVERS; BLADDER Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24264