Dr. Pant on the RAGNAR Trial of Erdafitinib in Biliary Tract Cancer

Shubham Pant, MD, associate professor, departments of Investigational Cancer Therapeutics and Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the rationale, trial design, and key efficacy and safety data from an expansion cohort of the phase 2 RAGNAR trial (NCT04083976) in biliary tract cancers.

Biliary tract cancer contains a variety of actionable genetic alterations, Pant begins. Recent developments in molecular profiling and the increasingly common use of next-generation sequencing (NGS) in clinical practice have improved the characterization of unique molecular tumor subtypes and subsequent selection of targeted therapies.

The open-label, single-arm RAGNAR trial was conducted to investigate the efficacy and safety of the FGFR-directed therapy erdafitinib (Balversa) in both adult and pediatric patients with advanced solid tumors and FGFR alterations, Pant says. Erdafitinib gained previous FDA approval for use in bladder cancer, but investigators often use the agent in biliary tract cancers, Pant notes. 

The study consisted of a molecular screening phase to identify patients with biliary tract cancer who also expressed an FGFR alteration, followed by treatment and then post-treatment follow-up. An expansion cohort was then performed in 35 pretreated patients with intrahepatic cholangiocarcinoma and FGFR1-4 mutations or fusions. 

Results showed that 60% of patients receiving erdafitinib experienced an overall response rate, reflecting a reduction of at least 30% in the sum of target legions, Pant states. Moreover, the disease control rate was 100% in these patients, and responses were observed regardless of co-occurring genomic alterations. Safety data were consistent with the known adverse event (AE) profile for erdafitinib, as well as other FGFR inhibitors, he continues. Twenty-five patients experienced treatment-related AEs (TRAEs) grade 3 or higher. TRAEs led to treatment discontinuation in 3 patients, and death in 0 patients. The most commonly observed AEs were hyperphosphatemia, diarrhea, and stomatitis, Pant concludes.