Study to Determine the Safety and Pharmacokinetics of DO-2 in Patients With Advanced or Refractory Solid Tumours

Exclusion Criteria17

• tumour harbouring other known oncogenic mutations promoting tumour growth
• major surgery within 3 weeks before enrolment
• chemotherapy (in the case of nitrosoureas and mitomycin C within 6 weeks), radiotherapy, immunotherapy, or any other study drug within 3 weeks before study drug administration
• antibody based cancer therapy within 4 weeks before administration of the first dose of DO-2
• patients who became progressive on previous treatment with a MET-kinase inhibitor
• patients with brain metastases are excluded unless all of the following criteria are met:
• CNS lesions are asymptomatic and previously treated
• No ongoing requirement for corticosteroids as therapy for CNS metastases
• Imaging demonstrates stability of disease \> 28 days from last treatment for CNS metastases
• leptomeningeal involvement (leptomeningeal carcinomatosis)
• history of uncontrolled heart disease including unstable angina, congestive heart failure, myocardial infarction within preceding 12 months, clinically significant rhythm or conduction abnormality, congenital long QT syndrome, obligate use of a cardiac pacemaker, QTc at screening greater than 450 milliseconds in males and greater than 470 milliseconds in females
• uncontrolled arterial hypertension despite appropriate therapy
• positive pregnancy test (urinary beta-hCG) at screening (applicable to women of child-bearing potential who are sexually active)
• mental status alteration or history of major psychiatric illness, which may potentially impair patient's compliance with study procedures
• signs and symptoms of active infection requiring systemic therapy
• other medical condition (e.g. pre-existing kidney dysfunction) that in the opinion of the investigator makes it undesirable for a patient to participate
• inability or unwillingness to swallow capsules and malabsorption syndrome or other condition that would interfere with enteral absorption