Fibroblast growth factor receptor (FGFR) inhibitor rogaratinib in patients with advanced pretreated squamous-cell non-small cell lung cancer over-expressing FGFR mRNA: the SAKK 19/18 phase II study

•Patients with advanced squamous-cell lung cancer have frequently tumor overexpression of fibroblast growth factor receptor (FGFR) messenger ribonucleic acid (mRNA).•Rogaratinib is a novel oral pan-FGFR inhibitor with a good safety profile and anti-tumor activity in early clinical trials.•Rogaratinib failed to improve PFS in patients with advanced squamous lung cell carcinomas overexpressing FGFR mRNA.•FGFR inhibitors in SQCLC remain a challenging field for which a more in-depth understanding of pathway crosstalks is essential. Patients with advanced squamous-cell lung cancer (SQCLC) frequently (46%) exhibit tumor overexpression of fibroblast growth factor receptor (FGFR) messenger ribonucleic acid (mRNA). Rogaratinib is a novel oral pan-FGFR inhibitor with a good safety profile and anti-tumor activity in early clinical trials as a single agent in FGFR pathway-addicted tumors. SAKK 19/18 determined clinical activity of rogaratinib in patients with advanced SQCLC overexpressing FGFR1-3 mRNA. Patients with advanced SQCLC failing standard systemic treatment and with FGFR1-3 mRNA tumor overexpression as defined in the protocol received rogaratinib 600 mg BID until disease progression or intolerable toxicity. A 6-months progression-free survival rate (6mPFS) ≤15% was considered uninteresting (H0), whereas a 6mPFS ≥38% was considered promising (H1). According to a Simon 2-stage design, 2 out of 10 patients of the first stage were required to be progression-free at 6 months. Comprehensive Genomic Profiling was performedusing the Oncomine Comprehensive Assay Plus (Thermo Fisher Scientific). Between July 2019 and November 2020, 49 patients were screened and 20 were classified FGFR-positive. Among a total of 15 patients, 6mPFS was reached in 1 patient (6.7%), resulting in trial closure for futility after the first stage. There were 7 (46.7%) patients with stable disease and 5 (33.3%) patients with progressive disease. Median PFS was 1.6 (95% CI 0.9-3.5) months and median overall survival (OS) 3.5 (95% CI 1.0-5.9) months. Most frequent treatment-related adverse events (TRAEs) included hyperphosphatemia in 8 (53%), diarrhea in 5 (33%), stomatitis in 3 (20%) and nail changes in 3 (20%) patients. Grade ≥3 TRAEs occurred in 6 (40%) patients. No associations between mutational profile and treatment outcome were observed. Despite preliminary signals of activity, rogaratinib failed to improve PFS in patients with advanced SQCLC overexpressing FGFR mRNA. FGFR inhibitors in S