Phase I Study of HL-085 in Patients With Advanced Solid Tumors

A Phase I, Single Arm, Dose Escalation Study to Evaluate Safety, Pharmacokinetics and Preliminary Efficacy of HL-085 in Subjects With Advanced Solid Tumors

The study drug, HL-085 is a MEK inhibitor with the potential indication for cancers. It is an oral medication to be given daily.

The purposes of this study is to find answers to the following research questions:

1. What is the highest tolerable dose of HL-085 that can be given to subjects when given orally (by mouth) on a twice daily basis?
2. What are the side effects of HL-085?
3. How much HL-085 is in the blood at specific times after dosing and how does the body get rid of the HL-085?

Inclusion Criteria:

1. Must have a pathologically documented solid tumor(s) that has relapsed from, or is refractory to standard treatment, or for which no standard treatment is available.
2. Must have at least one measurable lesion as defined by RECISTv1.1 criteria for solid tumors.
3. Must have received biological chemotherapy, immunotherapy or radiotherapy ≥4 weeks prior to starting the study treatment. Must have received small molecule chemotherapy ≥2 weeks or five half-lives (whichever is longer) prior to starting the study treatment.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
5. Life expectancy ≥3 months (as judged by the Investigator).
6. Must have adequate hematologic, hepatic and renal function.

Exclusion Criteria:

1. Have undergone or plan to have major surgery or experienced severe trauma ≤28 days prior to starting the study treatment.
2. Known hypersensitivity to IP ingredients or their analogues.
3. Prior therapy with a MEK-inhibitor
4. Receipt of any other investigational agent therapy within 4 weeks prior to starting study treatment.
5. Any concurrent therapy for cancer treatment.
6. Have active central nervous system lesion.
7. Receiving and unable to discontinue medication which are strong inducers, strong inhibitors or enzyme substrates of cytochrome P450 CYP2C9 and CYP2C19 from 14 days prior to treatment.
8. Grade 3 bleeding symptoms (NCI-CTCAE v5.0) within 4 weeks prior to starting study treatment.
9. Unable to swallow IP or has refractory nausea and vomiting, malabsorption, external biliary diversion, or any significant small bowel resection that may interfere with adequate absorption of IP.
10. ECG QTcB≥480msec in screening, or history of congenital long QT syndrome.
11. Left ventricular ejection fraction (LVEF) <50%.
12. History major cerebrovascular diseases within 6 months prior to enrollment.
13. Infectious diseases requiring systemic treatment.
14. History or current evidence of retinal diseases.
15. Have active/chronic infection with hepatitis C, or positive hepatitis B surface antigen (HBsAg), or active/chronic infection with human immunodeficiency virus (HIV).
16. Known active tuberculosis.
17. History of allogeneic bone marrow transplantation or organ transplantation.
18. Interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis.
19. Pregnant or breast-feeding females.
20. Previous or history of second malignancy within 5 years prior to study treatment
21. Other conditions which may increase the risk associated with study participation, or interfere with the evaluation of study results.