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

HUTCHMED

Status and phase

Completed

Phase 1

Conditions

Solid Tumor

Treatments

Drug: Epitinib

Study type

Interventional

Funder types

Industry

Identifiers

NCT02590952

2010-813-00CH1

Details and patient eligibility

About

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.

Enrollment

108 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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