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.

Abstract

e21119 Background: A substantial proportion of patients with squamous lung cell carcinoma (SQCLC) (46%) exhibit tumor overexpression of fibroblast growth factor receptor (FGFR) messenger ribonucleic acid (mRNA). Rogaratinib is a novel pan-FGFR inhibitor with anti-tumor activity in pre-clinical models as a single agent in FGFR pathway-addicted tumor models. Phase I data showed promising activity and good safety profile. The objective of the SAKK 19-18 trial was to determine clinical activity and safety of rogaratinib in patients with advanced SQCLC overexpressing tumor FGFR1-3 mRNA. Methods: Patients with metastatic SQCLC, previously treated with systemic treatment, overexpressing tumour FGFR mRNA were treated with rogaratinib 600 mg BID until progression of disease or drug intolerance. A rate ≤15% of PFS at 6 months was considered uninteresting, whereas a PFS rate at 6 months ≥38% was considered promising. Ten patients were needed in the first stage with at least 2 achieving 6 months PFS in order to continue the accrual. Results: Between May and November 2020, 49 patients were screened and 20 were classified FGFR positive. Among them15 patients were registered in the trial and the first 10 were assessed for the first stage analysis. Most commons treatment related adverse events (TRAEs) were hyperphosphatemia (60%), diarrhoea (20%), and dry mouth (20%). Grade ≥3 TRAEs occurred in 50% of the patents with Hypercalcemia being the most frequent one (20%). Among 10 first patients only 1 achieved 6 months PFS while 2 was the boundary required for continuing this trial. Conclusions: Despite preliminary signal of activity, rogaratinib failed to improve PFS in patients overexpressing tumor FGFR mRNA. Further studies on a more reliable biomarker are needed, the development of rogaratinib in SQCLC has been put on hold by Bayer and the SAKK 19/18 study was terminated early due to lack of efficacy. Clinical trial information: NCT03762122.