A Phase I Study of Epitinib(HMPL-813) in Patients With Advanced Solid Tumors

An Open-label, Multi-Centered, Dose Escalation Phase Ib Study (Expansion Stage) of Epitinib (HMPL-813) in Patients With Advanced Solid Tumors

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.

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