In the phase 2 FIDES-01 clinical trial, treatment with the FGFR inhibitor, derazantinib, led to an objective response rate of 24% in patients with FGFR2 gene fusion-positive advanced intrahepatic cholangiocarcinoma.
In the phase 2 FIDES-01 clinical trial, treatment with the FGFR inhibitor derazantinib, led to an objective response rate of 24% in patients with FGFR2 gene fusion–positive advanced intrahepatic cholangiocarcinoma (iCCA), according to topline results from cohort 1 announced in a press release by developer Basilea Pharmaceutica Ltd.1
“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 in FGFR2 gene fusion–positive iCCA patients, and the safety and tolerability data strengthen the evidence for derazantinib’s potential differentiation versus other FGFR inhibitors,” said Marc Engelhardt, MD, chief medical officer of Basilea Pharmaceutica Ltd, in a statement.
The disease control rate achieved with derazantinib was 72.8%, which was based on the percent of patients who achieved a partial response or stable disease.
In addition to response data, the topline results noted a median progression-free survival (mPFS) achievement of 6.6 months. This result was for 103 patients who had received at least 1 prior chemotherapy regimen who were enrolled in the intent-to-treat population in cohort 1. Twenty-one patients had a confirmed partial response. The mPFS was consistent with the published interim results, where the mPFS was 5.7 months (95% CI, 4.04-9.2), in a cohort of 29 patients.2
Safety data from cohort 1 also appeared consistent with the interim data. At a 300 mg once daily dose, the most common drug-related adverse events reported were hyperphosphatemia, asthenia, increased liver enzymes, nausea, dry mouth, dry eye, diarrhea, and dysgeusia. Notably, a low percentage (6%) of patients experienced drug-related adverse events, which were retinopathy, stomatitis, or hand-foot syndrome in 1% of patients each.1
FIDES-01 (NCT03230318) is part of a clinical trial series curated to develop derazantinib in different tumor types. In FIDES-02, a phase 1/2 trial (NCT04045613), derazantinib is being investigated as monotherapy and in combination with atezolizumab (Tecentriq) in patients with advanced urothelial cancer, including metastatic, or recurrent surgically unresectable disease, expressing FGFR genetic aberrations. New data from FIDES-02 are being presented during the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium.1,3 Additionally, derazantinib is being evaluated in the phase 1/2 FIDES-03 in combination with ramucirumab (Cyramza) and paclitaxel, or atezolizumab, in patients with advanced gastric cancer with FGFR genetic aberrations.1
Due to the antitumor activity and safety derazantinib has demonstrated early on in patients with iCCA, the drug holds Orphan Drug Designations from the FDA and from regulatory bodies in Europe.
“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. We are therefore particularly interested to see the first efficacy data on the combination of derazantinib with other anti-cancer agents in our urothelial and gastric cancer studies, which may allow us to further strengthen the evidence for its differentiation versus other FGFR inhibitors both from the efficacy and safety perspective. The upcoming data read-outs across different patient populations and indications both as monotherapy and combination therapy will also help us determine the optimal overall regulatory strategy for derazantinib,” Engelhardt stated.
1. Basilea reports positive topline results from phase 2 study FIDES-01 for derazantinib in FGFR2 gene fusion-positive patients with bile duct cancer (iCCA). News release. Basilea Pharmaceutica, Ltd. February 10, 2021. Accessed February 12, 2021. https://bit.ly/3agpqoE
2. Mazzaferro V, El-Rayes BF, Busset MD, et al. Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma. Br J Cancer. 2019; 120, 165–171. doi: 10.1038/s41416-018-0334-0
3. Basilea reports derazantinib/PD-L1 checkpoint inhibitor combination results from dose-finding part of FIDES-02 study in patients with solid tumors at ASCO GU symposium. News release. Basilea Pharmaceutica, Ltd. February 12, 2021. Accessed February 12, 2021. https://bit.ly/3aV9Uxq