Study of HL-085 in NRAS Mutant Advanced Melanoma

A Phase I/II, Single Arm, Dose Escalation and Cohort Expansion Study to Evaluate Safety, Preliminary Efficacy of HL-085 in Patients With NRAS Mutant Advanced Melanoma

This is a phase I/II, open-label, dose escalation study to evaluate tolerability, safety, pharmacokinetics and efficacy in patients with NRAS mutant advanced melanoma .

Inclusion Criteria:

1. Histologically or cytologically confirmed unresectable Stage III or Stage IV melanoma according to AJCC (Version 7, 2010).
2. Subjects must have NRAS mutation in melanoma.
3. Chemotherapy, immunotherapy or radiotherapy ≥ 4 weeks prior to starting the study treatment. Surgery (except for tumor biopsy) or severe trauma ≤ 14 days prior to starting the study treatment.
4. ECOG performance status of 0-1.
5. Life expectancy ≥ 3 months.
6. Ability to take the medicine orally.
7. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Prior therapy with a MEK-inhibitor
2. Patients with known hypersensitivity to study drug ingredients or their analogues.
3. Active central nervous system (CNS) lesion.
4. ECG QTcB≥480msec in screening, or history of congenital long QT syndrome.
5. Subjects with bleeding symptoms at Grade 3 (NCI-CTCAE v4.03) within 4 weeks prior to starting study treatment.
6. Uncontrolled concomitant diseases or infectious diseases.
7. Retinal diseases (Retinal Vein Occlusion (RVO) or Retinal pigment epithelial detachment (RPED) , et al.).
8. History of HIV,HCV,HBV infection.
9. Interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis will be excluded.
10. Serum HCG test is positive.
11. Other conditions that influence the results and increase the risk of study.