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.
Name: Epitinib
Description: The starting daily dose is 20 mg. Dose escalation will follow daily dose of 40 mg,80 mg, 120 mg, 160 mg, 200 mg, and 250 mg. A 3+3 design applies to this study. Patients will continue taking Epitinib until they experience intolerable adverse events or their diseases are confirmed to be progressed.Type: DrugEpitinib
Description: for each patient, adverse events are collected from the date of consent until 30 days after trial discontinuation
Measure: incidence of all types/grades of adverse events Time: from first patient in till 30 days after the last patient last visit. It is estimated that last patient last visit happens in Oct 2016.Description: Based on single-dose PK result, multi-dose stage subjects take epitinib either once a day or twice a day. For twice a day epitinib uptake, on day 1/14/28, PK samples are collected predose, 1, 4, 8, 12 hours post-dose in the morning and 4 hours post-dose in the evening. On day 2/3/7, PK samples are collected predose, 4, 12 hours post-dose in the morning and 4 hours post-dose in the evening. On day 15/29/56, PK samples are collected predose in the morning. For once a day epitinib uptake, on day 1/14/28 PK samples are collected predose, 0.5, 1, 2, 4, 6, 8, 12 hours post-dose. On day 7, PK samples are collected predose and 4 hours post-dose. On day 2/15/29/56, PK samples are collected predose in the morning.
Measure: Area under the plasma concentration versus time curve (AUC) Time: At single-dose stage (day 1-day 7): predose, 0.5,1, 2, 3, 4, 5, 6, 8,12,24, 36, 48, 72, 144 hours post-dose.Description: Based on single-dose PK result, multi-dose stage subjects take epitinib either once a day or twice a day. For twice a day epitinib uptake, on day 1/14/28, PK samples are collected predose, 1, 4, 8, 12 hours post-dose in the morning and 4 hours post-dose in the evening. On day 2/3/7, PK samples are collected predose, 4, 12 hours post-dose in the morning and 4 hours post-dose in the evening. On day 15/29/56, PK samples are collected predose in the morning. For once a day epitinib uptake, on day 1/14/28 PK samples are collected predose, 0.5, 1, 2, 4, 6, 8, 12 hours post-dose. On day 7, PK samples are collected predose and 4 hours post-dose. On day 2/15/29/56, PK samples are collected predose in the morning.
Measure: Peak Plasma Concentration (Cmax) Time: At single-dose stage (day 1-day 7): predose, 0.5,1, 2, 3, 4, 5, 6, 8,12,24, 36, 48, 72, 144 hours post-dose.Single Group Assignment
There is one SNP
On day 2/15/29/56, PK samples are collected predose in the morning.. 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). --- L858R ---
- 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 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). --- L858R ---