603TiP Phase II, open-label study of erdafitinib in adult and adolescent patients (pts) with advanced solid tumours harboring fibroblast growth factor receptor (FGFR) gene alterations

Abstract

The pan-FGFR tyrosine kinase inhibitor erdafitinib is approved by the US Food and Drug Administration for adults with locally advanced or metastatic urothelial carcinoma and susceptible FGFR3/2 alterations who have progressed during or after ≥ 1 line of platinum-containing chemotherapy. FGFR alterations are potential oncogenic drivers that have been reported in many solid tumours in adult and pediatric pts. Because of limited response to standard of care options in patients failing systemic therapy, there is strong rationale to assess the safety and efficacy of erdafitinib in adolescent and adult pts with advanced solid tumours and FGFR alterations. This phase II open-label study (RAGNAR/42756493CAN2002; NCT04083976) will include pts aged ≥ 12 years with histologically confirmed unresectable locally advanced or metastatic solid tumours (except urothelial) harboring predefined FGFR mutations or fusions. Eligibility screening includes molecular screening for FGFR alterations by central or local next-generation sequencing assays and other clinical criteria. Pts will enroll into either a broad panel cohort (BPC) of target FGFR alterations or an exploratory cohort (EC) for FGFR alterations not meeting BPC criteria. ∼280 pts (BPC, n = 240; EC, n = 40) will be enrolled. The primary efficacy end point is overall response rate (ORR) per Independent Review Committee. Secondary end points include investigator-assessed ORR, duration of response, disease control rate, progression-free survival, overall survival, safety, pharmacokinetics, and health-related quality of life. Safety assessments include adverse events, vital signs, electrocardiograms, physical examinations, laboratory tests, performance status assessment, growth assessments in adolescents, and ophthalmologic examination. Starting in December 2019, pts will be enrolled at ∼158 sites in 15 countries. Results of this study will provide efficacy and safety data for erdafitinib across multiple solid tumours with FGFR alterations and evaluate potential benefit of targeting underlying altered biology of FGFR irrespective of tumour histology in adult and adolescent pts. NCT04083976. Writing assistance was provided by Sally Hassan, PhD, of Parexel, and was funded by Janssen Global Services, LLC. Janssen Research & Development, LLC.