Interim Analysis of the FIDES-01 Study

Derazantinib is a potent oral inhibitor of FGFR1, FGFR2, and FGFR3 that is being investigated in the phase 2 FIDES-01 clinical trial of patients with advanced intrahepatic cholangiocarcinoma (CCA) harboring FGFR2 fusions or rearrangements.

At the 2022 ASCO GI Cancers Symposium, interim results on the efficacy and safety of derazantinib in previously treated patients with locally advanced or metastatic intrahepatic CCA harboring FGFR2 mutations or amplifications (cohort 2) from the ongoing phase 2 FIDES-01 study were presented.

The patients in cohort 2 of the FIDES-01 study had locally advanced or metastatic intrahepatic CCA or mixed histology tumors (ie, combined hepatocellular CCA), centrally confirmed FGFR2 mutations or amplifications, and an ECOG performance status of 0-1. Patients received derazantinib 300 mg daily until disease progression, death, or unacceptable adverse events. The primary end point of this analysis was the proportion of patients alive and free of disease progression at 3 months. Data cutoff was August 31, 2021.

In this interim analysis, the intention-to-treat population included 28 patients who had ≥1 postbaseline tumor assessment (or disease progression or died) per the investigator’s assessments. The median age was 64 years; the majority (61%) of patients were women, 36% were aged ≥56 years, 61% had extrahepatic metastasis, and 93% had short FGFR2 fusion variants. The most common short variants were F276C (6 patients) and C382R (4 patients); amplifications without concurrent fusions were reported in 2 patients.

The efficacy population included 23 patients; patients received a median 5.2 cycles of derazantinib for 28 days (mean dose intensity, 98%). At a median follow-up of 5.2 months, the investigator-assessed best overall response rate included 2 (8.7%) partial responses and 15 (65.2%) stable diseases, resulting in a disease control rate of 74% (95% confidence interval [CI], 51.6-89.8). Although only infrequent responses were achieved in this cohort, tumor shrinkage occurred in the majority of patients with FGFR2 mutations or amplifications. The median progression-free survival was 7.3 months (95% CI, 3.5-16.7), and the probability of being progression free was 76.3% (95% CI, 51.9-89.4) at 3 months and 50.3% (95% CI, 21.7-73.4) at 6 months.

The safety population included 131 patients, including 103 patients with FGFR2 fusions from a previous analysis plus the current population of 28 patients with FGFR2 mutations or amplifications. Overall, the safety profile in this analysis was consistent with that previously reported for patients with FGFR2 fusion. In terms of the FGFR-inhibitor class effects, the results showed a low incidence of nail problems (8%), stomatitis (2%), hand-foot syndrome (2%), hyponatremia (2%), and retinal side effects (2%).

Based on these results, Dr Javle and colleagues concluded that derazantinib treatment provided clinical benefit to patients with advanced intrahepatic CCA harboring FGFR2 mutations or amplifications whose disease progressed after ≥1 lines of standard chemotherapy, and the safety profile was consistent with what has been seen in previous studies.

Source: Javle MM, Abou-Alfa GK, Macarulla T, et al. Efficacy of derazantinib in intrahepatic cholangiocarcinoma patients with FGFR2 mutations or amplifications: interim results from the phase 2 study FIDES-01. American Society of Clinical Oncology Gastrointestinal Cancers Symposium 2022. Abstract 427.