Derazantinib: an investigational drug for the treatment of cholangiocarcinoma

ABSTRACT

Introduction

This review evaluates the clinical role of fibroblast growth factor receptor 2 (FGFR2) inhibition with derazantinib in patients with intrahepatic cholangiocarcinoma (iCCA) harboring actionable oncogenic FGFR2 fusions/rearrangements, mutations and amplifications. FGFR inhibitors such as derazantinib are currently being evaluated to address the unmet medical need of patients with previously treated, locally advanced or metastatic iCCA harboring such genetic aberrations.

Areas covered

We summarize the pharmacokinetics, and the emerging safety and efficacy data of the investigational FGFR inhibitor derazantinib. We discuss the future directions of this novel therapeutic agent for iCCA.

Expert Opinion

Derazantinib is a potent FGFR1‒3 kinase inhibitor which also has activity against colony stimulating factor-1‒receptor (CSF1R) and vascular endothelial growfth factor receptor‒2 (VEGFR2), suggesting a potentially differentiated role in the treatment of patients with iCCA. Derazantinib has shown clinically meaningful efficacy with durable objective responses, supporting the therapeutic potential of derazantinib in previously treated patients with iCCA harboring FGFR2 fusions/rearrangements, mutations and amplifications. The clinical safety profile of derazantinib was well manageable and compared favorably to the FGFR inhibitor class, particularly with a low incidence of drug-related hand-foot syndrome, stomatitis, retinal and nail toxicity. These findings support the need for increased molecular profiling of cholangiocarcinoma patients.

KEYWORDS:

• CSF1R kinase inhibition
• derazantinib
• FGFR1‒3 kinase inhibition
• FGFR2 amplifications
• FGFR2 fusions
• FGFR2 mutations
• intrahepatic cholangiocarcinoma
• VEGFR2 kinase inhibition

Funding

This paper was not funded

Article highlights

• Cholangiocarcinoma is emerging as a disease entity with actionable molecular targets, broadening the therapeutic options and helping to improve patient outcomes beyond the limited available standard of care treatment.

• Molecular profiling of cholangiocarcinoma patients has identified several therapeutic targets such as FGFR2fusions/rearrangements, mutations and amplifications.

• Derazantinib is a reversible FGFR1‒3 kinase inhibitor with additional activity against CSF1R and VEGFR2, and it is a promising agent for patients with iCCA harboring FGFR2 genetic aberrations, following previous chemotherapy.

• Phase I and II studies have shown that derazantinib has a manageable safety profile and provides clinically meaningful and durable responses translating into progression-free survival improvements.

• Clinical studies in patients with iCCA and other tumor indications are currently underway to explore the full potential of derazantinib as monotherapy and in combination with either immunotherapy or chemotherapy.

This box summarizes key points contained in the article.

Acknowledgments

Editorial support was provided by Alison Coletta, Principal Medical Writer, Effective Medical. Graphics support was provided by Charles Fair and Kara Nyberg, PhD, both Global Healthcare Marketing and Communications.

Reviewer disclosures

One reviewer has been a consultant for Basilea. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose

Declaration of interest

The authors are employees and own stocks of the company Basilea Pharmaceutica International Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.