Derazantinib Shows Clinical Benefit, Manageable Safety Profile in Patients With Cholangiocarcinoma


Derazantinib is an investigational oral inhibitor of FGFR1, FGFR2, and FGFR3 in patients with locally advanced or metastatic intrahepatic cholangiocarcinoma.

Treatment with derazantinib, an FGFR inhibitor, produced a meaningful clinical benefit with a manageable safety profile in patients with locally advanced or metastatic intrahepatic cholangiocarcinoma (iCCA), according to data from the phase 2 FIDES-01 study (NCT03230318) presented at the 2022 ESMO Congress. Derazantinib is an investigational oral inhibitor of FGFR1FGFR2, and FGFR3 being developed under the FIDES program. The program includes patients with urothelial and gastric cancer harboring various FGFR genetic aberrations as well.

The study results showed that patients with iCCA harboring FGFR2 fusions in cohort 1 (n = 103) had a median progression-free survival (PFS) of 7.8 months (95% CI, 5.5-8.3) and a 6-month PFS rate of 53.9% (95% CI, 42.8%-63.7%). Patients with iCAA with FGFR mutations or amplifications (cohort 2; n = 44) had a median PFS of 8.3 months (95% CI, 3.5-16.7) and a 6-months PFS rate of 53.9% (95% CI, 42.8%-63.7%).

At 12 months follow-up, the PFS rate was 18.8% (10.1-29.5) in cohort 1 and 44.5% (20.4%-66.1%) in cohort 2.

Further, cohort 1 showed an overall response rate (ORR) of 22.3% (95% CI, 14.7%-31.6%) and a disease control rate (DCR) of 75.7% (95% CI, 66.3%-83.6%). Cohort 2 showed an ORR of 6.8% (95% CI, 1.4%-18.7%) and a DCR of 63.6% (95% CI, 47.8%-77.6%). Median overall survival (OS) was 17.2 months in cohort 1 compared with 15.9 months in cohort 2.

Stable disease was achieved in 53.4% and 56.8% across both cohorts, respectively. Progressive disease rates were 15.5% in cohort 1 and 20.5% in cohort 2, with a median duration of response of 6.4 months in cohort 1 and 5.6 months in cohort 2.

One patient in cohort 2 experienced a complete response (CR) and had nonmeasurable disease per RECIST 1.1 criteria compared with no patients experiencing a CR in cohort 1. There was no postbaseline assessment for 7.8% of patients with FGFR2 fusions and for 15.9% of patients with FGFR2 mutations or amplifications.

According to the study authors, activated FGFRs show promise as a therapeutic target because deregulation of the FGFR signaling pathway is implicated in iCCA. An estimated 10% to 16% of patients with iCCA have FGFR2 fusions with mutations and amplifications in 4% of patients, whereas smaller series show an incidence range of 8% to 13%.

The study investigators enrolled patients 18 years of age and older with locally advanced or metastatic iCCA or with combined hepatocellular-cholangiocarcinoma. Eligibility requirements included an ECOG performance status of 0 or 1 and adequate hematological laboratory values. Patients in both cohorts self-administered derazantinib 300 mg daily until progression, unacceptable toxicity, or withdrawal.

In cohort 1, treatment cycles were 28 days with patients administered a median of 7 cycles compared with cohort 2 receiving 5. Tumors were measured by CT or MRI every 8 weeks for the first 6 months and every 12 weeks after to determine ORR.

The primary end point of cohort 1 was ORR and the primary end point of cohort 2 was PFS. Median patient age was 56 years (range, 28-84) in cohort 1 and 63.5 years (range, 28-80) in cohort 2. Across both cohorts, the majority of patients enrolled were women (65% and 57%, respectively).

At least 1 adverse event (AE) was reported by 88% of patients overall, with 32% reporting a grade 3 or higher event. The most common AEs of any grade were hyperphosphatemia/blood phosphorus increased (35%), fatigue/asthenia (33%), nausea (32%), dry mouth (27%), and dry eye (24%). Spikes in AST and ALT were common grade 3 or higher AEs, as 10% of patients experienced an AST increase and 9% experienced an ALT increase.

The drug was found to have a manageable safety profile with a low amount of the FGFR-inhibitor-class effects, such as nail toxicities (7.5%), stomatitis (2.0%), retinal events (1.4%), and palmar-plantar erythrodyesthesia (1.4%).


Borad MJ, 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. doi:10.1016/j.annonc.2022.07.087.

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