The FIDES-01 clinical trial was a phase 2, open-label, single-arm study evaluating the efficacy of derazantinib as a second-line therapy in patients with inoperable or advanced intrahepatic cholangiocarcinoma (iCCA) with FGFR2 gene fusions, mutations, or amplifications. Derazantinib is a potent kinase inhibitor, and similar drugs in this class have been FDA approved for the treatment of CCAs with FGFR alterations. Disruptions in FGFR2 are relatively common in patients with iCCA, with FGFR2 fusions present in approximately 15% of patients and another 5% having mutations or amplifications in FGFR2.
Patients with advanced iCCA characterized as either FGFR fusions or FGFR mutations or amplifications and ≥1 previous line of chemotherapy were treated with derazantinib 300 mg daily (N = 143). FGFR anomalies were confirmed and characterized via fluorescence in situ hybridization or next-generation sequencing. Primary end points for the FIDES-01 trial were objective response rate (ORR) for FGFR2 fusions as assessed by central radiology review, and progression-free survival (PFS) for FGFR2 mutations or amplifications as assessed either radiographically or by survival status.
Median age for the study population was 59 years, and approximately half of the participants had ≥2 previous lines of therapy. Tumor response and safety data were collected from 103 patients in the FGFR2 fusions cohort. In the FGFR2 mutations or amplifications cohort, safety was assessed in 40 patients, and response in 31 patients. These results were presented at the 2022 ESMO GI congress.
In all, 98% of the 103 patients with FGFR2 fusions discontinued treatment, as did 78% of the 40 patients in the FGFR2 mutations or amplifications cohort. In the FGFR2 fusion group, ORR was 21.4%, and the disease control rate (DCR) was 75.7% (95% confidence interval [CI], 66.3-83.6). Median PFS was 8.0 months (95% CI, 5.5-8.3), and median overall survival (OS) was 17.2 months (95% CI, 12.5-22.4). Patients with FGFR2 mutations or amplifications had a confirmed ORR of 6.5% (95% CI, 0.8-21.4), and the DCR was 58.1% (95% CI, 39.1-75.5). Median PFS in these patients was 8.3 months (95% CI, 1.9-16.7), and median OS was 15.9 months (95% CI, 8.4-not estimable). The most common adverse events (AEs; any grade) observed were hyperphosphatemia (37%), asthenia/fatigue (34%), nausea (30%), transaminase elevations (29%), dry mouth (27%), and dry eye (23%). The majority of AEs were grade 2 or less.
Preliminary data from this small, genetically defined population support the use of derazantinib as a clinically meaningful and targeted second-line therapy for patients with iCCA whose tumors are characterized by genetic aberrations in FGFR2.
Sources: Borad M, Javle M, Shaib WL, et al. Efficacy of derazantinib in intrahepatic cholangiocarcinoma (iCCA) patients with FGFR2 fusions, mutations or amplifications. Ann Oncol. 2022;33(suppl 7):S567-S568.
Borad MJ, Javle M, Shaib WL, et al. Efficacy of derazantinib in intrahepatic cholangiocarcinoma (iCCA) patients with FGFR2 fusions, mutations or amplifications. European Society for Medical Oncology World Congress on Gastrointestinal Cancer 2022. Abstract 59P.
