Safety and Tolerability of ODM-203 in Subjects With Advanced Solid Tumours

• Written informed consent
• Male and female subjects over 18 years of age
• Subjects with histologically or cytologically confirmed locally advanced or metastatic tumours. Subjects in Part 2 to have a tumour/genetic aberration.
• Availability of tumour sample for genetic analysis
• Adequate haemopoietic, hepatic and renal function
• Eastern Cooperative Oncology Group performance status of 0 to 1
• Serum mineral levels phosphate: 2.5 mg/dl; calcium: 8.8 mg/dl; magnesium: 1.2 mg/dl; potassium: 11.7 mg/dl; sodium: 299mg/dl.
• Recovery from reversible adverse events of previous systemic anti-cancer therapies to baseline or grade 1 with the exception of alopecia;stable neuropathy of grade 2 induced by previous cancer treatment
• Life expectancy of 12 weeks or more

Exclusion Criteria:

• Any prior anti VEGFR/FGFR treatment related AE that in the judgement of the investigator is considered severe/life threatening
• Subjects receiving warfarin
• Active central nervous system metastases not controlled by prior surgery/radiotherapy and/or low dose steroids for 4 weeks or more
• Subjects with current evidence of endocrine alteration of calcium-phosphate homeostasis
• Concomitant therapies known to increase serum phosphorus and/or calcium levels that cannot be discontinued or switched to a different therapy are not permitted within 14 days before the first dose of ODM-203.
• Significant cardiovascular conditions/circumstances as follows:
• a active or unstable cardio/cerebro-vascular disease
• b Uncontrolled hypertension (systolic blood pressure ≥ 150mmHg and/or diastolic blood pressure ≥ 90mg Hg with optimised antihypertensive therapy.
• c history of severe arrhythmia, familial arrhythmia, conduction abnormality or congenital long QT syndrome
• dConcomitant therapies known to prolong the QT interval and associated with a risk of Torsades de Pointes are not permitted within 7 days before the first dose of ODM 203
• e Repeatable prolongation of QTcF interval ≥ 450 msec or any clinically significant abnormality in the ECG at screening in 2 out of 3 recordings
• f Left ventricular ejection fraction \<50% at screening
• Subjects who received systemic anticancer treatment prior to the first dose of ODM-203 within the following timeframes: less than 28 days since the last dose of antineoplastic therapy and/or 28 days of wide field radiotherapy or 14 days of limited field radiation for palliation
• Major surgery or serious infection within 21 days of the first dose of ODM-203
• Known gastrointestinal disease or a procedure that may affect absorption of ODM 203
• Serious concurrent medical condition or psychiatric illness
• History and/or current evidence of ectopic mineralisation/calcification
• Known active or past history of other primary malignancy
• Female of child bearing potential
• Female of child bearing potential or male subject with a female partner of child bearing potential who does not agree to use effective contraception during the study and for 3 months after the last dose of ODM 203
• Known hypersensitivity to the study treatment excipients
• Any condition which in the opinion of the investigator would impair the subject's ability to comply with the study procedures
• Participation in another interventional clinical trial/ concurrent treatment with any investigational drug within 4 weeks prior to the start of treatment with ODM 203