Erdafitinib in Patients With Advanced Solid Tumors With <i>FGFR</i> Alterations (RAGNAR): Results of Tumor-Specific Analyses and Secondary Cohorts.

Abstract

Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, is approved for second-line treatment of locally advanced or metastatic urothelial carcinoma with susceptible <i>FGFR3</i> alterations. Primary histology-agnostic analysis from the phase II RAGNAR study (ClinicalTrials.gov identifier: NCT04083976) indicated a clinical benefit with erdafitinib in Broad Panel Cohort (BPC) patients. We present tumor-specific updated efficacy and safety results from the BPC and tumor-agnostic findings from the Exploratory and Pediatric Cohorts of RAGNAR. The Broad Panel, Exploratory, and Pediatric Cohorts enrolled patients with target (selected) <i>FGFR</i> alterations, nontarget <i>FGFR</i> alterations, and any <i>FGFR</i> alterations, respectively. Adults and pediatric patients (6 years and older) with advanced, unresectable, or metastatic disease who progressed after ≥1 prior line of systemic therapy and exhausted standard therapies were eligible. Erdafitinib 3-8 mg once daily (with possible uptitration) was administered orally until disease progression or intolerable toxicity. Objective response rates (ORRs) in the BPC were 10.0% (3 of 30) for high-grade glioma, 26.1% (6 of 23) for non-small cell lung cancer, 28.6% for (2 of 7) low-grade glioma, 31.3% (5 of 16) for breast cancer, 33.3% (5 of 15) for head and neck squamous cell carcinoma, 55.6% (10 of 18) for pancreatic cancer, and 100% (5 of 5) for salivary gland cancer. The ORR was 3.8% (2 of 53) in the Exploratory Cohort. In the Pediatric Cohort (n = 11), there were one responder and seven patients with durable stable disease. Treatment-related adverse events (TRAEs) were consistent with the known safety profile of erdafitinib. Pediatric-specific TRAEs included epiphysiolysis and limb fracture. Encouraging activity was observed for erdafitinib across tumor types in patients with advanced malignancies and selected <i>FGFR</i> alterations who have exhausted treatment options. More limited activity was observed for erdafitnib in the Exploratory Cohort.