a phase i study of epitinib(hmpl-813) in patients with advanced solid tumors

Conditions: Solid Tumor

Summary: epitinib (hmpl-813) is a selective egfr tyrosine kinase inhibitor. epitinib has demonstrated strong inhibitory effects on multiple tumors with overexpressed egfr or sensitive egfr mutations in pre-clinical setting. this first-in-human study is conducted to assess the maximum tolerated dose (mtd) and dose-limiting toxicity(dlt), safety and tolerability, pharmacokinetics (pk), and preliminary anti-tumor activity of epitinib.


Eligibility criteria:
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) * age 18-70 * ecog 0-2, and no worse within 7days * life expected \> 12 weeks * written informed consent form voluntarily * for dose expansion cohort, subjects must be eligible for the following inclusion criteria: * egfr sensitizing mutation in exon 19 deletion or exon 21(l858r). * histologically or cytologically confirmed advanced nsclc with brain metastasis. no prior brain radiotherapy or brain metastasis progressed after brain radiotherapy delivered assessed by recist 1.1. * no prior egfr-tki treatment. or subjects who treated with egfr-tki developed brain lesions during egfr-tki therapy or the existing brain lesions progressed but with stable extra-cranial lesions. * treatment failure of prior systemic chemotherapy for locally advanced or metastasized nsclc or intolerance to chemotherapy. or subjects with disease relapse after treated with adjuvant or neo-adjuvant chemotherapy. * with at least one measurable disease ( recist 1.1). exclusion criteria: * lab testing within 2 weeks before enrolled, and anc\<1.5×10 9/l, platelet\<75×10 9/l, or hb\<9g/dl, * serum total bilirubins \> uln, alt/ast≥uln without liver metastasis, or alt/ast≥2.5uln with liver metastasis * serum creatinine \>1.5uln or creatinine clearance \<40ml/min * diastolic systolic pressure≥140mmhg or systolic diastolic pressure≥90mmhg whatever anti-hypertension drug used, * serum potassium \<4.0mmol/l(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. * unrecovered from any previous therapy related toxicity to ctcae 0 or 1or unrecovered from any previous surgery * known dysphagia or drug malabsorption * active infections such as acute pneumonia, hepatitis b immune-active periodphase * ocular surface diseases or dry eye syndrome * skin disease with obvious symptoms and signs * significant cardiovascular disease, including ii-iv atrioventricular block, and acute myocardial infarction within 6 months, significant angina or coronary artery bypass graft within 6 months * 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

Keywords: safety, pk