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Poster display

1656 - Phase 1 study of ODM-203, a selective dual FGFR/VEGFR inhibitor, in patients with advanced solid tumours

Date

10 Oct 2016

Session

Poster display

Presenters

Jordi Rodon

Citation

Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368

Authors

J. Rodon1, K. Peltola2, A. Azaro1, E. Castanon Alvarez3, C. Garratt4, H. Leskinen5, H. Bjorklund6, A. Ruck4, C. Massard3, P. Bono2

Author affiliations

  • 1 Medical Oncology, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 2 Comprehensive Cancer Center, HUCH Helsinki University Central Hospital, 00029 - Helsinki/FI
  • 3 Drug Development Department (ditep), Institut Gustave Roussy, 94800 - Villejuif/FR
  • 4 Oncology And Critical Care, Orion Pharma, NG1 1AH - Nottingham/GB
  • 5 Drug Safety, Orion Pharma, Helsinki/FI
  • 6 Drug Metabolism, Orion Pharma, Turku/FI
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Resources

Abstract 1656

Background

Inhibitors of fibroblast growth factor receptors (FGFR) are being developed for treatment of solid tumours with FGFR genetic alterations. ODM-203 is a small molecule with balanced inhibitory effects on both FGFR 1-4 and VEGFR 1-3 subtypes. We present updated results from the first-in-man study.

Methods

ODM-203 was evaluated in an open 3 + 3 dose escalation design to identify the maximum tolerated dose (MTD), dosed daily in a 4 week cycle. Subsequent cohorts are evaluating the optimal dose and alternative dosing schedules. Pharmacokinetics and safety variables were closely monitored during the first 4 weeks with tumour response according to RECIST recorded every 8 weeks on treatment. Patients continued ODM-203 treatment until disease progression or dose limiting toxicity (DLT).

Results

31 patients (median age 54, range 28-80 years) with advanced solid tumours received ODM-203 treatment in doses between 50-800mg once/day during the dose escalation phase. Patients had various primary tumours, some having FGFR alterations. One cholangiocarcinoma patient with FGFR2 fusion has been treated for more than 1 year. One DLT (corneal keratopathy) was recorded at 800mg/day but MTD was not identified. A single grade 4 AE (lipase increase) was reported. Most AE's reported were grade 1-2, the most common ones being increased bilirubin (61%), diarrhoea (36%), alopecia (29%), jaundice (26%), increased phosphate (26%), stomatitis (23%) and epistaxis (19%). Increased bilirubin was due to UGT1A1 inhibition by ODM-203 and resolved in all cases upon dose reduction/interruption. Plasma ODM-203 exposure was variable. There were 3 partial responses (RCC, ovarian and FGFR mutated salivary gland cancer) and 5 further patients achieved target lesion reduction. In addition, 4 patients had disease stabilisation of at least 24wk. Further follow-up and results of ongoing dose schedule evaluation will also be presented.

Conclusions

In ODM-203 treated patients there was preliminary evidence of promising anti-tumour activity although FGFR-aberrant tumours were not preselected. ODM-203 elicited on-target adverse effects in addition to bilirubin changes. An expansion study in patients with FGFR-aberrant or VEGFR sensitive tumours is ongoing.

Clinical trial identification

NCT02264418

Legal entity responsible for the study

Orion Corporation, Orion Pharma

Funding

Orion Corporation, Orion Pharma

Disclosure

J. Rodón: Consulting/Advisory role: Novartis, Lilly/ImClone, Servier. K. Peltola: Employment: Orion Corporation. Stock: Faron Pharmaceuticals. Consulting/honoraria: Lilly, Sanofi, Novartis, Baxalter, Bristol Myers Squibb, Pfizer. C. Garratt, H. Leskinen, H. Bjorklund, A. Ruck: Employee of Orion Pharma. P. Bono: Honoraria: MSD, Orion Pharma, Novartis, Bristol Myers Squibb, Pfizer. Research funding: Novartis. All other authors have declared no conflicts of interest.

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