HMPL-309Open-label, Dose Escalation Phase I Study of Theliatinib (HMPL-309,Xiliertinib) in Patients With Advanced Solid Tumors

Study start date: April 1, 2015

Inclusion Criteria: * Histopathology confirmed solid tumors * Failed to standard treatment or no standard treatments for uncontrolled, recurrent and/or metastatic advance tumor (whatever previous surgery conditions) Dose-escalation stage: \<300mg/day cohort no requiremnet for pathological pattern \>300mg/day cohort required NCSLC, head and net squamous carcinoma, or oesophageal carcinoma Dose-expansion stage required oesophageal carcinoma * Age 18-75 * performance status of 0, or 1, and no worse within 7days * Life expected \>3 months * written informed consent form voluntarily Exclusion Criteria: * Lab testing within 1 week before enrolled, hemoglobin \<9 g/dL or , platelet count \< 750,000/mm3 and\<150000/mm3, * Total bilirubin≥1.5× the upper limit of normal, * Serum creatinine higher than normal range * Diastolic pressure≥150mmHg or systolic pressure≥100mmHg whatever anti-hypertension drug used, * Serum potassium (whenever potassium implemented) , serum calcium(ionic or albumin-type calcium) or serum magnesium outside normal ranges(whenever implemented) * Within previous 4 weeks treated by systemic anti-tumor therapy, or radiotherapy, immune therapy, biological or hormonal therapy, and clinical trials. But exclude the below therapy, Prostate cancer treated by hormonal therapy such as GnRH(gonadotropin-releasing hormone) analogue or antagonist Hormone replacement therapy or oral contraceptive Palliative radiotherapy for bone metastasis within 2 weeks * Prior documental evidence of resistance to EGFR-TKI (epidermal growth factor receptor-tyrosine kinase inhibitors) * Unrecovered from any previous therapy related toxicity to≤ CTCAE(Common Toxicity Criteria for Adverse Effects) 0 or 1or unrecovered from any previous surgery * Any CNS(central nervous system) metastasis with uncontrolled symptoms * Known dysphagia or drug malabsorption * Active infections such as acute pneumonia, hepatitis B active period * APTT (activated partial thromboplastin time) and/or INR(international normalized ratio), PT≥2 the upper limit of normal(not including patients treated by anticoagulation treatment) * ocular surface diseases or dry eye syndrome * skin disease with obvious symptoms and signs * significant cardiovascular disease, including II-IV atrioventricular block, acute myocardial infarction within 6 months, significant angina or Coronary artery bypass graft * Known existing interstitial lung disease * Female patients who are pregnant or feeding, or childbearing potential patient with pregnant testing positive * Any abnormal of clinical and laboratory so that patients unsuitable to attend the trial sine in the opinion of the investigator * Patients unable to comply with the protocol since significant psychological or psychogenic abnormal