study to determine the safety and pharmacokinetics of do-2 in patients with advanced or refractory solid tumours

Conditions: Adult Solid Tumor; Advanced Solid Tumor; Refractory Tumor; Non-small Cell Lung Cancer; Non-small Cell Carcinoma; Lung Cancer; Hereditary Renal Papillary Cancer

Summary: 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.

in part 1, a simon design 3 accelerated titration design will be followed. one patient will be enrolled per cohort, until grade 2 toxicity is observed. three sequential patients per cohort will be enrolled thereafter, with a minimum of 1 week between first dose administration in the first patient and the subsequent ones, in those latter cohorts.

Eligibility criteria:
inclusion criteria: * 18 years or older * histologically or cytologically confirmed advanced or refractory solid tumour and no longer eligible for approved, available standard therapies. tumour types must have: 1. proven met activating mutations, determined by previous next generation sequencing (ngs), whole exome sequencing (wes), whole transcriptome sequencing (wts) or other genomic analysis methods, or 2. proven amplification (≥ 10 copies) on archived tumour tissue. or 3. hereditary renal papillary cancer * measurable disease in accordance with recist 1.1 * eastern cooperative oncology group (ecog) performance status ≤ 1 * adequate bone marrow function, without the support of cytokines * adequate liver function * adequate renal function * agree to follow the contraception requirements of the trial * signed 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 enrollment * 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: 1. cns lesions are asymptomatic and previously treated 2. no ongoing requirement for corticosteroids as therapy for cns metastases 3. 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