Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
Early clinical experience with the pan-FGFR inhibitor rogaratinib in patients with non-small cell lung cancer selected based on FGFR mRNA expression levels.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr e20661)
Author(s): Markus Joerger, Byoung Chul Cho, Nicolas Mach, Cristina Caballero, Ross A. Soo, Manfred Wirth, Cyrus Sayehli, Alejandro Navarro, Bhumsuk Keam, Ana-Maria Piciu, Sebastian Bender, Hendrik Nogai, Peter Ellinghaus, Martin H. Schuler; Cantonal Hospital St. Gallen, St. Gallen, Switzerland; Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea; Hôpitaux Universitaires de Genève, Geneva, Switzerland; Hospital General Universitario de Valencia, Valencia, Spain; National University Cancer Institute, Singapore, Singapore; University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; University Hospital Würzburg, Würzburg, Germany; Vall d'Hebron University Hospital/Vall d´Hebron Institute Oncolgy (VHIO), Barcelona, Spain; Department of Internal Medicine, Hemato-Oncology, Seoul National University Hospital, Seoul, South Korea; Bayer, Munich, Germany; Bayer AG, Pharmaceuticals Division, Berlin, Germany; Bayer AG, Pharmaceuticals Division, Wuppertal, Germany; University Hospital Essen, Essen, Germany
Background: FGFR1 gene amplifications are observed in squamous (sq) non-small cell lung cancer (NSCLC) and may suggest tractable oncogenic dependency. However, their value in predicting clinical activity of FGFR inhibitors is unclear. We explored tumor FGFR1-3 mRNA expression levels to select patients (pts) for treatment with rogaratinib, an oral, potent, small-molecule inhibitor of FGFR1-4. The first-in-human study of rogaratinib included pts with all NSCLC histologies. Methods: Pts with refractory advanced NSCLC were screened for elevated FGFR1-3 mRNA levels by RNA in situ hybridization (RNAscope) and NanoString assay in fresh or archival tumor samples, and FGFR1-3 overexpression was defined by pre-specified cut-offs. Pts received rogaratinib 800 mg BID on a continuous 21-day cycle. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors v1.1 after cycles 2, 5, and 8. Results: 260 NSCLC biopsies were screened for FGFR1-3 tumor mRNA expression; 244 (93.8%) were evaluable. FGFR1-3 mRNA overexpression was found in 47% of sq NSCLC, and only 14% of non-sq NSCLC, with FGFR3 being the most commonly overexpressed subtype. 40 FGFR mRNA-positive pts were enrolled and treated. Rogaratinib was well tolerated; hyperphosphatemia (75%), diarrhea (53%), and decreased appetite (35%) were the most frequent treatment-emergent adverse events. Events were mostly mild or moderate. 36 treated pts were evaluable for response. The overall response rate was 5.6% (2 partial responses, 1 lasting for > 16 months). Disease control rate was 64%. Disease stabilization was seen in pts with mRNA overexpression across all FGFR subtypes and also in pts who failed prior lines of therapy, including anti-PD-L1. Molecular studies are ongoing to identify additional predictors of response to improve pt selection. Conclusions: Rogaratinib has a favorable safety and tolerability profile and clinical activity in pts with refractory FGFR1-3 tumor mRNA-positive NSCLC. It has potential for further exploration in combination with other agents. A clinical trial is currently enrolling FGFR mRNA-overexpressing pts with advanced and pre-treated sq NSCLC. Clinical trial information: NCT03762122