Efficacy and safety of erdafitinib in adults with cholangiocarcinoma (CCA) with prespecified fibroblast growth factor receptor alterations (FGFRalt) in the phase 2 open-label, single-arm RAGNAR trial: Expansion cohort results.
Authors: Pant Shubham , Schuler Martin H. , Iyer Gopa , Doi Toshihiko , Qin Shukui , Tabernero Josep , Arnold Dirk , Gutierrez Martin , Prenen Hans , Folprecht Gunnar , Winter Helen , Cosman Rasha , Zibetti Dal Molin Graziela , Xia Qi , Najmi Saltanat , Hammond Constance , Thomas Shibu , Triantos Spyros , Sweiti Hussein , Loriot Yohann 
Published: January 2023

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Background: Erdafitinib (erda) is an oral selective pan-FGFR tyrosine kinase inhibitor approved to treat locally advanced or metastatic urothelial carcinoma in adults with susceptible FGFR3/2alt who have progressed during or after ≥1 line of platinum-containing chemotherapy . Interim results from the ongoing phase 2 RAGNAR study (NCT04083976) demonstrated tumor agnostic efficacy and safety of erda in adults with advanced solid tumors harboring prespecified FGFRalt after failure of standard therapies (Loriot Y, et al. J Clin Oncol 2022;40(suppl 16):3007). Here we report results from an expansion cohort of the RAGNAR study that enrolled only patients (pts) with CCA. Methods: Adults (aged ≥18 y) with advanced or metastatic CCA with predefined FGFR1-4alt (mutations/fusions [excluding amplifications] based on local/central test) and documented disease progression on ≥1 prior line of systemic therapy received oral erda until disease progression or intolerable toxicity. The primary end point is objective response rate (ORR) by independent review committee (IRC). Secondary end points include duration of response (DOR), disease control rate (DCR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), investigator-assessed efficacy end points, and safety. Results: At data cutoff (median follow-up 20.4 mo), 35 pts with CCA received erda (median age 57 y [range 40-74], median 2 prior systemic therapy [range 1-6]); 90.9% had visceral metastasis, and 17.1% responded to last line of therapy. ORR by IRC was 60.0% (95% CI 42.1-76.1). Median time to onset of response was 1.5 mo (range 1.1-8.2). Responses were observed in pts harboring FGFR mutations and fusions and in pts with co-occurring genomic alterations. Median DCR and CBR were 100.0% (95% CI 90.0-100.0) and 71.4% (95% CI 53.7-85.4), respectively. Median DOR, PFS, and OS were 5.6 mo (95% CI 2.8-8.3), 8.4 mo (95% CI 5.5-9.7), and 18.7 mo (95% CI 8.9-not evaluable), respectively. Investigator-assessed efficacy end points were aligned with IRC results. The most common treatment-emergent adverse events (TEAEs) were hyperphosphatemia (82.9%), diarrhea (80.0%), and stomatitis (74.3%). The majority of pts (80.0%) had grade ≥3 TEAEs, the most common being anemia (22.9%), stomatitis (20.0%), and acute kidney injury (11.4%); 42.9% had serious TEAEs; 11.4% discontinued treatment due to TEAEs. No treatment-related deaths were observed. Conclusions: Data from the CCA expansion cohort of the phase 2 RAGNAR study demonstrate robust efficacy of erda in heavily pretreated adults with CCA harboring prespecified FGFR fusions or mutations, irrespective of co-occurring genomic alterations. Safety data were consistent with the known safety profile of erda. Clinical trial information: NCT04083976 .