Combined Analysis of RAGNAR and LUC2001 Trials: Effectiveness and Safety of Erdafitinib in Individuals Diagnosed With Advanced or Metastatic CCA and FGFR Mutations

Erdafitinib, an oral selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, is approved in the United States for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma with specific FGFR3 alterations whose disease has progressed on or after ≥1 lines of prior systemic therapy. The primary analysis from the phase 2 RAGNAR study and phase 2a LUC2001 study demonstrated efficacy with erdafitinib and a manageable safety profile in patients with cholangiocarcinoma (CCA) and alterations in FGFR. A pooled analysis of patients with CCA treated with erdafitinib from both studies was presented at ASCO 2024.

RAGNAR (NCT04083976) was a single-arm, multicenter, phase 2 study in 15 countries that included participants who had exhausted all standard treatment options, and LUC2001 (NCT02699606) was an open-label, multicenter, phase 2 a study in Asian patients (China, Taiwan, and South Korea) that included individuals with advanced solid tumors who had undergone at least 1 prior line of therapy. Patients were treated with erdafitinib (8 mg daily, with the option for dose escalation) until disease progression or adverse events on continuous 21-day cycles in the RAGNAR study and on 28-day treatment cycles in the LUC2001 study. Those with CCA and specific FGFR alterations were grouped for an efficacy analysis (objective response rate [ORR] by independent review committee [IRC], duration of response [DOR], progression-free survival, overall survival) and safety evaluation.

At the time of data cutoff, erdafitinib had been administered to 78 patients (RAGNAR, 66; LUC2001, 12). The median follow-up for efficacy was 14.7 months. The median age was 56 years, with 60.3% being female, 47.4% White, and 38.5% Asian. Patients had received a median of 2 prior lines of therapy; 92.0% had visceral metastases, and 16.7% had responded to previous treatment. FGFR2 alterations were present in 93.6% of patients, with 91.0% having fusions. The ORR by IRC was 55.1%. The median time to onset of response was 1.7 months. Observations of responses were noted in patients with modified FGFR2 and FGFR3 genes, spanning across both FGFR mutations and fusions. The median DOR, progression-free survival, and overall survival were 6.9 (95% confidence interval [CI], 4.37-8.61), 8.5 (95% CI, 6.83-9.72), and 18.1 (95% CI, 13.40-24.28) months, respectively. The most common treatment-emergent adverse events (TEAEs) included hyperphosphatemia (82.1%), stomatitis (69.2%), palmar-plantar erythrodysesthesia (51.3%), diarrhea (50.0%), and dry mouth (48.7%). Serious TEAEs were reported in 15.4% of patients, with 7.7% discontinuing treatment due to an adverse event. There were no treatment-related deaths observed.

The combined analysis of the RAGNAR and LUC2001 studies demonstrates the strong effectiveness of erdafitinib in treating a wide range of patients with advanced or metastatic CCA and specific FGFR fusions or mutations. The safety data also align with the established safety profile of erdafitinib.

Source:

Pant S, Park OJ, Su W, et al. Efficacy and safety of erdafitinib in patients with advanced or metastatic cholangiocarcinoma and FGFR alterations: pooled analysis of RAGNAR and LUC2001 studies. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; abstract 4121.