Efficacy and Safety of Derazantinib in Patients with Previously Treated iCCA with an FGFR2 Fusion or Rearrangement: The FIDES-01 Study

Web Exclusives — December 20, 2021

Derazantinib is a potent FGFR1-3 kinase inhibitor that was evaluated in the phase 2 FIDES-01 study (ClinicalTrials.gov Identifier: NCT03230318) of patients with advanced intrahepatic cholangiocarcinoma (iCCA) who harbor FGFR2 fusions/rearrangements. The primary efficacy and safety results of the completed FGFR2 fusion–positive cohort from the study were presented at the 2021 European Society for Medical Oncology Annual Conference.

The study enrolled patients with locally advanced or metastatic iCCA, documented disease progression following ≥1 lines of prior treatment, and centrally confirmed FGFR2 fusion. Eligible patients received derazantinib 300 mg once daily. The primary end point was objective response rate (ORR), as assessed by independent central review per RECIST version 1.1. Secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Data cutoff was April 25, 2021.

In the intent-to-treat population, a total of 103 patients were enrolled in the FGFR fusion–positive cohort. The median participant age was 56 years. The majority (65%) of patients in this cohort were female, 50% were aged ≥56 years, and 47% had received ≥2 prior treatment lines. At data cutoff, 91% of patients had discontinued treatment.

At a median follow-up of 12.6 months, centrally confirmed ORR of 21.4% was achieved, including 22 partial responses. Overall, 56 patients achieved stable disease, for a DCR of 75.7%; the median DOR was 6.4 months. Median PFS was 8.0 months; median OS was 15.9 months (data still immature at the data cutoff). Time to progression was 8.1 months, which was longer than treatment received prior to study initiation (4.5 months). ORR and PFS benefits extended to predefined patient subgroups.

The most common drug-related adverse events (all grades) occurring in ≥20% of patients included hyperphosphatemia and/or a laboratory value worsening from baseline (76%), asthenia/fatigue (34%), transaminase elevations (31%), nausea (29%), dry eye (30%), dry mouth (23%), and diarrhea (20%). Grade ≥3 adverse events were reported in 35% of patients, including transaminase elevations (10%), fatigue/asthenia (5%), and hyperphosphatemia (4%).

Based on these study results, the investigators concluded that the study met its primary end point and that derazantinib showed durable objective responses with a manageable safety profile in patients with iCCA who harbor FGFR2 fusions.


Droz Dit Busset M, Shaib WL, Mody K, et al. Derazantinib for patients with intrahepatic cholangiocarcinoma harboring FGFR2 fusions/rearrangements: primary results from the phase II study FIDES-01. Ann Oncol. 2021;32(suppl_5):S376.

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