Clinical trial NCT02590952: A Phase I Study of Epitinib(HMPL-813) in Patients With Advanced Solid Tumors
Official title: An Open-label, Multi-Centered, Dose Escalation Phase Ib Study (Expansion Stage) of Epitinib (HMPL-813) in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Keywords: safety, PK
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2015-10-29
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: incidence of all types/grades of adverse events
timeFrame: 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.
Secondary outcomes:
measure: Objective Response Rate
timeFrame: An average of one year
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: 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.
measure: Peak Plasma Concentration (Cmax)
timeFrame: 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.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong General Hospital
Study officials:
affiliation: Hutchison Medipharm Limited
name: Rongjun Liu, M.D.
role: STUDY_CHAIR
References:
citation: Zhou Q, Wang M, Zhang H, Hong Q, Liu X, Lu P, Su W, Wu YL. Safety and Efficacy of Epitinib for EGFR-Mutant Non-Small Cell Lung Cancer With Brain Metastases: Open-Label Multicentre Dose-Expansion Phase Ib Study. Clin Lung Cancer. 2022 Sep;23(6):e353-e361. doi: 10.1016/j.cllc.2022.03.014. Epub 2022 May 7.