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

This study is a first-in-human, open-label, 2-part, Phase 1 dose escalation study of DO-2, administered orally to patients with advanced or refractory solid tumours, with MET aberrations, and no available, approved therapeutic alternative.

Inclusion Criteria:18 years or olderhistologically or cytologically confirmed advanced or refractory solid tumour and no longer eligible for approved, available standard therapies. Tumour types must have:proven MET activating mutations, determined by previous next generation sequencing (NGS), whole exome sequencing (WES), whole transcriptome sequencing (WTS) or other genomic analysis methods, orproven amplification (≥ 10 copies) on archived tumour tissue. orHereditary Renal Papillary CancerEastern Cooperative Oncology Group (ECOG) performance status ≤ 2adequate bone marrow function, without the support of cytokinesadequate liver functionadequate renal functionagree to follow the contraception requirements of the trialsigned informed consent, indicating study patients understand the purpose of and procedures required for the study and are willing to participate in the study.Exclusion Criteria:major surgery within 3 weeks before enrollmentchemotherapy (in the case of nitrosoureas and mitomycin C within 6 weeks), radiotherapy, immunotherapy, or any other study drug within 3 weeks before study drug administrationantibody based cancer therapy within 4 weeks before administration of the first dose of DO-2patients with brain metastases are excluded unless all of the following criteria are met:CNS lesions are asymptomatic and previously treatedNo ongoing requirement for corticosteroids as therapy for CNS metastasesImaging demonstrates stability of disease > 28 days from last treatment for CNS metastasesleptomeningeal 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 femalesuncontrolled arterial hypertension despite appropriate therapypositive 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 proceduressigns and symptoms of active infection requiring systemic therapyother medical condition (e.g. pre-existing kidney dysfunction) that in the opinion of the investigator makes it undesirable for a patient to participate