Study of HL-085 in NRAS Mutant Advanced Melanoma

Study Overview
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Brief Summary
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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 .

Official Title
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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

Conditions
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Melanoma

Intervention / Treatment
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* Drug: HL-085


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed unresectable Stage III or Stage IV melanoma according to AJCC (Version 7, 2010). Subjects must have NRAS mutation in melanoma. 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. ECOG performance status of 0-1. Life expectancy ≥ 3 months. Ability to take the medicine orally. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Prior therapy with a MEK-inhibitor Patients with known hypersensitivity to study drug ingredients or their analogues. Active central nervous system (CNS) lesion. ECG QTcB≥480msec in screening, or history of congenital long QT syndrome. Subjects with bleeding symptoms at Grade 3 (NCI-CTCAE v4.03) within 4 weeks prior to starting study treatment. Uncontrolled concomitant diseases or infectious diseases. Retinal diseases (Retinal Vein Occlusion (RVO) or Retinal pigment epithelial detachment (RPED) , et al.). History of HIV,HCV,HBV infection. Interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis will be excluded. Serum HCG test is positive. Other conditions that influence the results and increase the risk of study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HL-085<br>HL-085 will be administered as BID with specified dose. | Drug: HL-085<br>* HL-085 is one MEK inhibitor.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | Number of Treatment-Related Adverse Events as Assessed by CTCAE v4.03 during the study period | Duration of the study, estimated to be approximately 24 months. | 
| Maximum tolerated dose (MTD) | The dose level immediately below the dose level at which ≥ 2 patients from a cohort of 3 to 6 patients experience a dose-limiting toxicity (DLT) | DLTs within the first cycle of therapy (up to 35 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) as measure of efficacy | Efficacy estimated as the Objective Response Rate (ORR) , which is the sum of Partial Response (PR) and Complete Response (CR) as determined by RECIST 1.1 | Duration of the study, estimated to be approximately 24 months. | 
| Area under the plasma concentration versus time curve (AUC) | AUC of HL-085 following single and repeated dosing | Duration of the study, estimated to be approximately 24 months | 
| Peak Plasma Concentration (Cmax) | Cmax of HL-085 following single and repeated dosing | Duration of the study, estimated to be approximately 24 months | 
| Time to maximum observed plasma drug concentration (Tmax) | Tmax of HL-085 following single and repeated dosing | Duration of the study, estimated to be approximately 24 months. | 
| Half-life (T1/2) | T1/2 of HL-085 following single and repeated dosing | Duration of the study, estimated to be approximately 24 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, NRAS