Phase I/IIa, open-label, multicentre study to evaluate the optimal dosing and safety of ODM-203 in patients with advanced or metastatic solid tumours

Abstract

BackgroundGenetic alterations in fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR) signalling are observed in various tumours. We report a first-in-human phase I/IIa trial evaluating tolerability, pharmacokinetics and preliminary antitumour activity of ODM-203, a novel FGFR and VEGFR inhibitor.MethodsOpen-label, non-randomised, multicentre, phase I/IIa dose escalation and expansion study in patients with advanced or metastatic solid tumours.ResultsOverall, 84 patients received treatment; optimal tablet dose was found to be 400 mg/day with food. All patients experienced at least one adverse event; the majority (89.2%) were grade 1 or 2% and 70.4% were considered treatment related. The most commonly reported events were bilirubin increase-related events (75%) and diarrhoea (50%).Overall response rate was 9.2% and median progression-free survival was 16.1 and 12.4 weeks for patients with aberrant or non-aberrant FGFR tumours. Median time on treatment was 10.1 weeks for all patients and 14.5 weeks for patients who received 400 mg tablets.ConclusionThis study suggests ODM-203 400 mg/day results in sufficient plasma concentrations and acceptable tolerability in most patients. Preliminary signs of therapeutic activity of ODM-203 in patients with solid tumours was observed.Trial registration numberNCT02264418.

Leveraging patient derived models of FGFR2 fusion positive intrahepatic cholangiocarcinoma to identify synergistic therapies

“…It should be noted that G3BP2 is a somewhat novel fusion partner with FGFR2, identified in only one patient previously 32 , yet its relevance was clearly illustrated in these data. While there are 16 well-characterized fusion partners in FGFR fusion-positive malignancies, recent high-throughput sequencing efforts have detected 37% to be novel 33 .…”

Recent progress on vascular endothelial growth factor receptor inhibitors with dual targeting capabilities for tumor therapy

“…In vitro and in vivo pieces of evidence have proven the significant tumor suppression role (TGI = 92%) of 29 in FGFR-dependent cell lines RT4 [89]. Notably, it has been evaluated in clinical trials for solid tumor therapy (NCT02264418) [90].…”

Small molecule inhibitors targeting the cancers

“…ODM‐203 is a pan‐VEGFR/FGFR inhibitor and has shown preliminary signs of therapeutic activity in solid tumors with acceptable tolerability (NCT02264418). 739 More researches are needed to verify the safety and effectiveness of ODM‐203. In general, dual inhibitors can theoretically increase efficacy and reduce side effects, but the practical application remains to be verified.…”

“…It is now under stage II trial for cervical cancer (NCT04395612). ODM‐203 is a pan‐VEGFR/FGFR inhibitor and has shown preliminary signs of therapeutic activity in solid tumors with acceptable tolerability (NCT02264418) 739 . More researches are needed to verify the safety and effectiveness of ODM‐203.…”