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Cholangiocarcinoma News

Derazantinib Beneficial in Patients with Intrahepatic Cholangiocarcinoma and FGFR2 Fusions: Early Results from FIDES-01

March 2021, Vol 2, No 1

In February 2021, Basilea Pharmaceuticals reported early results from the phase 2 FIDES-01 clinical trial (NCT03230318), which is evaluating the efficacy of derazantinib, an investigational small-molecule FGFR1-3 inhibitor, in patients with inoperable or advanced intrahepatic cholangiocarcinoma (CCA) and FGFR2 gene fusions or FGFR2 gene mutations or amplifications. Derazantinib also inhibits the colony-stimulating factor 1 receptor kinase (CSF1R). CSF1R-mediated signaling is important for the maintenance of tumor-promoting macrophages.

The FIDES-01 study includes 2 cohorts. This report presents the early results from cohort 1 of the study, which includes patients with inoperable or advanced intrahepatic CCA and FGFR2 gene fusions. Enrollment into cohort 1 has been completed. Enrollment into cohort 2, which is evaluating the efficacy of derazantinib in patients with intrahepatic CCA and FGFR2 gene mutations or amplifications, is ongoing.

In total, 103 patients with intrahepatic CCA and FGFR2 gene fusions who had received at least 1 previous chemotherapy regimen were enrolled in the intent-to-treat population in cohort 1. The patients received once-daily oral 300-mg derazantinib, until disease progression or until unacceptable adverse events.

The early results from cohort 1 showed an objective response rate (ORR) of 20.4%, which included 21 patients with a confirmed partial response. ORR has been predefined as the primary efficacy end point for cohort 1 and has been assessed through an independent central radiology review. The disease control rate (ie, patients with a partial response or stable disease) was 72.8%, and the median progression-free survival was 6.6 months.

These results for cohort 1 are not yet fully mature; 12 patients are continuing to receive derazantinib, including 3 patients with a partial response.

Consistent with previous data, derazantinib has a manageable safety profile. The most common drug-related adverse events were hyperphosphatemia, asthenia/fatigue, increased liver enzymes, nausea, dry mouth, dry eye, diarrhea, and dysgeusia. Overall, 6% of the patients had treatment-related adverse events in the nails, and 1% of patients, each, had retinopathy, and stomatitis or hand-foot syndrome.

“We are very pleased that the positive topline results from the first cohort of the FIDES-01 study provide the clinical proof of concept for derazantinib as monotherapy in its first indication, although the data are not fully mature yet, and a number of patients are still continuing their treatment. The efficacy results shown with derazantinib are consistent with the efficacy seen with FGFR inhibitors as a class…and the safety and tolerability data strengthen the evidence for derazantinib’s potential differentiation versus other FGFR inhibitors,” said Marc Engelhardt, MD, Basilea’s Chief Medical Officer.

“We expect the publication of a number of interim and topline results across the entire FIDES clinical program throughout 2021 and 2022. Based on its unique kinase inhibition profile, derazantinib has potential for enhanced activity in combination therapy,” Dr Engelhardt added.

In a previous phase 1/2 study, derazantinib demonstrated efficacy and manageable safety in patients with intrahepatic CCA,1 for which the FDA granted derazantinib an orphan drug designation.

  1. Mazzaferro V, El-Rayes BF, Droz dit Busset M, et al. Derazantinib (ARQ87) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma. Br J Cancer. 2019;120:165-171.

FDA Accepts 2 New Drug Applications for Therapies for Cholangiocarcinoma with Gene Alterations

In December 2020, the FDA accepted a New Drug Application (NDA) for infigratinib, an FGFR1-3 inhibitor, for the treatment of cholangiocarcinoma (CCA) with FGFR2 fusion. The FDA granted a priority review for this NDA.

In March 2021, the FDA accepted an NDA for ivosidenib (Tibsovo), an IDH1 inhibitor, for the treatment of patients with CCA and IDH1 mutation.

Related Items

FDA Grants Accelerated Approval to Infigratinib for Metastatic Cholangiocarcinoma
June/July 2021, Vol 2, No 2
The FDA granted accelerated approval to the kinase inhibitor infigratinib (Truseltiq) for the treatment of adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma (CCA) that harbors an FGFR2 fusion or other rearrangement.
Futibatinib in Intrahepatic Cholangiocarcinoma with FGFR2 Fusions or Rearrangements: Primary Results of FOENIX-CCA2 Presented at AACR 2021
June/July 2021, Vol 2, No 2
The primary results of the phase 2 FOENIX-CCA2 clinical trial of futibatinib in patients with previously treated intrahepatic cholangiocarcinoma (CCA) and FGFR2 fusions or rearrangements were presented by Lipika Goyal, MD, MPhil, Assistant Professor of Medicine, Massachusetts General Hospital, Boston, at the 2021 Annual Meeting of the American Association for Cancer Research (AACR).

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