HL-085 in NRAS-mutated Advanced Melanoma

Study Overview
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Brief Summary
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This was an open-label, single-arm, multi-center phase II clinical study, aimed at investigating the efficacy and safety of HL-085 capsule in the treatment of advanced melanoma patients with NRAS mutation.

Detailed Description
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This was an open-label, single-arm, multi-center phase II clinical study, aimed at investigating the efficacy and safety of HL-085 capsule in the treatment of advanced melanoma patients with NRAS mutation. The primary objective was to evaluate the objective response rate (ORR) of oral HL-085 capsule in patients with advanced melanoma harboring NRAS mutation. The secondary objectives were to evaluate the progression-free survival (PFS), disease control rate (DCR), duration of remission (DOR), 1-year survival rate, overall survival (OS) and safety.

Official Title
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A Single-arm, Multi-center Phase II Clinical Study to Evaluate the Efficacy and Safety of HL-085 in Advanced Melanoma Patients With NRAS Mutation

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: Aged 18 Years or older (male or female). Patients have histologically or cytologically confirmed Unresectable stage III or IV melanoma; Able to provide the genetic test report with documented NRAS mutation at baseline. At least one target lesion as per RECIST v1.1 criteria. Previous chemotherapy, immunotherapy, or radiotherapy must have been completed at least 4 weeks prior to study drug administration, and all related toxic reactions (with the exception of alopecia) must have been resolved (to Grade ≤1 or baseline) prior to study drug administration. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Life expectancy > 3 months. No major surgery (excluding baseline tumor biopsy) or major trauma occurred at least 14 days prior to study drug administration. Exclusion Criteria: Patients with active central nervous system (CNS) lesions (i.e., radiological evidence of instability, symptomatic lesions) should be excluded. Note: Patients receiving stereotactic brain radiotherapy or surgery who have shown no brain disease progression over a period of 3 months or longer are eligible for inclusion. Patients had received any other study treatment within the past 4 weeks prior to study drug administration. Inability to swallow the capsule, refractory nausea and vomiting, malabsorption, extracorporeal biliary shunt, or any small intestinal resection that would preclude adequate absorption of the study drug. ECG QTcB ≥ 480 msec (adjusted by Bazetts formula) during screening, or a history of congenital long QT syndrome. Bleeding symptoms of Grade 3 as defined by the National Cancer Institute General Terminology Standard for Adverse Events (NCI CTCAE V5.0) within the past 4 weeks prior to study initiation. One of the following situations occurs within the past 6 months prior to administration of study drug: myocardial infarction, severe/unstable angina, coronary artery/peripheral artery bypass grafting, symptomatic congestive heart failure, serious arrhythmia, uncontrolled hypertension, cerebrovascular accident, or transient ischemic attack, or symptomatic pulmonary embolism. Current use of other anti-cancer drugs (hormone therapy was acceptable). Uncontrolled concomitant diseases or infectious diseases. Patients have retinal vein occlusion (RVO), retinal pigment epithelial detachment (RPED) or other retinal diseases previously or currently.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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>12 mg BID HL-085 | Drug: HL-085<br>* HL-085 capsule administered orally twice daily (BID) in a 21-day treatment cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate (ORR) | To evaluate the objective response rate (ORR) of patients with advanced melanoma harboring NRAS mutation. ORR by RECIST v1.1 following treatment with HL-085 | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival (PFS) | To evaluate the progression-free survival (PFS), disease control rate (DCR), duration of remission (DOR) of patients with advanced melanoma harboring NRAS mutation after HL-085 treatment. | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HL-085, MEK inhibitor, NRAS mutation, advanced melanoma