Preliminary results of molecular screening for FGFR alterations (alts) in the RAGNAR histology-agnostic study with the FGFR-inhibitor (FGFRi) erdafitinib.

Abstract

4081 Background: FGFR alts (mutations and fusions) have been reported in multiple advanced solid tumors at varying frequencies. These alts may function as oncogenic drivers of disease independent of the underlying tumor type. RAGNAR is an ongoing phase 2, histology-agnostic trial investigating the efficacy and safety of erdafitinib, a selective pan-FGFRi, in patients (pts) with advanced solid tumors and FGFR alts. Little is known about the incidence, diversity or predominant FGFR alts across solid tumors in the clinical setting. Here, we provide an update on molecular screening and enrollment in the primary analysis population. Methods: Pts with advanced solid tumors were molecularly screened for eligible FGFR alts via central next generation sequencing (NGS) or review of local NGS reports. Underlying tumor type, FGFR alts, demographics and key disease characteristics were collected at baseline. Results: From Nov 2019 to Jan 2021, 5758 pts were molecularly screened (central or local) in 15 countries. 191 pts (3.3%) fulfilled primary analysis molecular eligibility criteria; 110 pts were enrolled. Among pts enrolled, 14 (12.7%) had central screening and 96 (87.3%) had local NGS reports. Eligible FGFR alts were identified in 19 tumor types, including rare cancers and ones (eg, pancreatic) with a very low prevalence of FGFR alts in genomic databases (Table). Median age was 57 y, and 19 pts (17.3%) were < 40 y. Gender distribution was even. Conclusions: Findings from molecular screening in the RAGNAR study indicate a wide range of FGFR-altered tumor types, including a notable number of cancers where eligible FGFR alts were considered exceedingly rare (eg, pancreatic). These results demonstrate the feasibility of conducting clinical trials on pts with rare genetic alts by adopting a histology-agnostic design and using both central testing and local NGS reports for molecular screening. This approach also helps investigate rare tumors, where histology-specific trials are challenging. Efficacy and safety results from the RAGNAR study will help define the benefit of erdafitinib in FGFR-altered advanced solid tumors. Clinical trial information: NCT04083976. [Table: see text]