A Prospective, Open-Label, Multicenter, Real-World Study to Evaluate the Efficacy and Safety of Tunlametinib in Patients With NRAS-Mutant Advanced Melanoma

This study is a prospective, open-label, multicenter, real-world clinical study designed to evaluate the efficacy and safety of tunlametinib in patients with NRAS-mutant advanced melanoma who have failed prior anti-PD-1/PD-L1 therapy.

The study consists of a screening period (from the subject signing the informed consent form to enrollment, no more than 28 days), a treatment period (treatment discontinuation is defined as the inability to continue treatment for any reason, such as confirmed disease progression per imaging, intolerable toxicity despite dose adjustment, initiation of new anti-tumor therapy, death, or withdrawal for any reason), and treatment completion and follow-up period (including safety visits and survival follow-up).

Subjects' eligibility will be determined based on information collected within 28 days prior to enrollment. Subjects who meet the study criteria will enter the treatment period. This study plans to enroll 110 subjects with NRAS-mutant advanced melanoma:

Tunlametinib will be administered at a dose of 12 mg orally, twice daily, continuously, in 4-week treatment cycles. Study treatment will continue until the occurrence of intolerable toxicity, PD, withdrawal of consent, initiation of new anti-tumor therapy, death, or when the investigator judges the risk outweighs the benefit, or the study is terminated/ends (whichever occurs first). Survival follow-up will continue after treatment discontinuation until the subject's death.

• Dose adjustments for tunlametinib are permitted and must be performed in a stepwise manner.
• In case of intolerance, the 12 mg dose should first be reduced to 9 mg twice daily, and then to 6 mg twice daily.
• Dose re-escalation depends on the specific situation. If tolerability improves significantly after dose reduction due to reasons such as AE intolerance, and the AE leading to dose reduction resolves to ≤ Grade 1 or baseline level, and no other intolerable toxicities occur after at least 6 weeks of treatment at the lower dose level, the previous dose level may be resumed. For example, if the dose is continuously reduced from 12 mg to 6 mg, re-escalation to 9 mg is recommended; re-escalation to 12 mg is generally not recommended.