HL-085 in NRAS-mutated Advanced Melanoma

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.

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.