hl-085 in nras-mutated advanced melanoma

Conditions: Melanoma

Summary: 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.

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.

Eligibility criteria:
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.

Keywords: hl-085 mek inhibitor nras mutation advanced melanoma