Tunlametinib for NRAS‑mutant advanced melanoma after PD‑1/PD‑L1 therapy

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 will test whether the oral drug tunlametinib helps adults with NRAS‑mutant advanced melanoma who did not respond to anti‑PD‑1/PD‑L1 therapy.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 110 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: tunlametinib
• Locations: 1 site (Shanghai)
• Trial ID: NCT07445022 on ClinicalTrials.gov

What this trial studies

This is a prospective, open‑label, multicenter real‑world study planning to enroll about 110 adults with histologically or cytologically confirmed NRAS‑mutant locally advanced or metastatic melanoma who have failed prior anti‑PD‑1/PD‑L1 therapy. Participants will take tunlametinib 12 mg orally twice daily in continuous 4‑week cycles, with dose adjustments allowed for toxicity. Treatment continues until confirmed disease progression, intolerable toxicity, initiation of new anti‑tumor therapy, withdrawal of consent, death, or investigator decision, and survival follow‑up continues after discontinuation. Eligibility is confirmed during a screening period up to 28 days before enrollment and safety visits are included during follow‑up.

Who should consider this trial

Good fit: Adults (≥18 years) with locally advanced or metastatic melanoma, documented NRAS mutation, prior failure of anti‑PD‑1/PD‑L1 therapy, ability to take oral medication, and willingness to comply with study procedures.

Not a fit: Patients without an NRAS mutation, those who are pregnant or breastfeeding, those currently enrolled in other investigational drug trials, or individuals judged by investigators to be unsuitable for targeted therapy are unlikely to benefit from this treatment.

Why it matters

Potential benefit: If successful, tunlametinib could provide an effective oral targeted option that shrinks tumors or delays progression for patients with NRAS‑mutant melanoma after PD‑1/PD‑L1 therapy has failed.

How similar studies have performed: Other MEK inhibitors have shown modest activity in NRAS‑mutant melanoma with limited durable responses, and tunlametinib‑specific real‑world evidence remains limited.

Eligibility criteria

Inclusion Criteria:

* Aged ≥18 years (inclusive), male or female;
* Patients with histologically or cytologically confirmed locally advanced or metastatic melanoma;
* Prior genetic testing results showing positive NRAS mutation;
* Patients who have failed prior anti-PD-1/PD-L1 therapy;
* Able to take oral medications;
* Voluntarily participate and sign the informed consent form, expected to have good compliance, and able to cooperate with the study according to the protocol requirements.

Exclusion Criteria:

* Currently participating in other clinical trials of drugs;
* Patients who are pregnant or breastfeeding;
* Other conditions deemed unsuitable for targeted therapy after multidisciplinary discussion;
* Other conditions considered inappropriate for inclusion by the investigator, such as familial or social factors that may affect the safety of the subject or the collection of data.

Where this trial is running

Shanghai

• Fudan University Shanghai Cancer Center — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Yu Wang

Conditions Melanoma Advanced