Belvarafenib plus cobimetinib for NRAS-mutant advanced or metastatic melanoma

A Phase 2, Multicenter, Single-Arm Study of Belvarafenib (HM95573) in Combination With Cobimetinib in Patients With Locally Advanced or Metastatic NRAS-Mutant Melanoma

This trial will test whether taking belvarafenib with cobimetinib can shrink tumors or control disease in adults with NRAS‑mutant advanced or metastatic melanoma.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 19 Years and up
• Sex: All
• Sponsor: Hanmi Pharmaceutical Company Limited (industry)
• Drugs / interventions: Cobimetinib
• Locations: 10 sites (Seongnam-si, Gyeonggi-do and 9 other locations)
• Trial ID: NCT07449754 on ClinicalTrials.gov

What this trial studies

This is a Phase 2, open‑label, single‑arm, multicenter trial of oral belvarafenib combined with cobimetinib given in 28‑day cycles to adults with NRAS‑mutant locally advanced or metastatic melanoma. The study will enroll patients who have measurable disease, adequate organ function, and an ECOG performance status of 0–2 and who have not received prior RAF/MEK/ERK inhibitors. Key outcomes include objective response rate, disease control rate, duration of response, time to progression, progression‑free survival, overall survival, and safety. Safety monitoring will include assessments for retinal, cardiac, bleeding, hematologic, hepatic, and renal adverse events.

Who should consider this trial

Good fit: Adults (≥19 years) with histologically or cytologically confirmed locally advanced or metastatic melanoma harboring an NRAS mutation, at least one measurable lesion, ECOG ≤2, adequate organ function, and no prior RAF/MEK/ERK inhibitor therapy are ideal candidates.

Not a fit: Patients with prior RAF/MEK/ERK inhibitor exposure, significant retinal or cardiac disease, recent major bleeding (CTCAE Grade ≥3 within 4 weeks), or inadequate organ function are unlikely to be eligible or to benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could provide a new targeted option that shrinks tumors or prolongs disease control for patients with NRAS‑mutant melanoma.

How similar studies have performed: MEK inhibitor monotherapy has shown only modest activity in NRAS‑mutant melanoma, and combining a RAF‑targeted agent with a MEK inhibitor is a relatively novel approach with limited published clinical data to date.

Eligibility criteria

Key Inclusion Criteria:

* Have histologically, cytologically confirmed locally advanced or metastatic melanoma for which no adequate standard of care exists, or for which standard of care has failed or is not tolerated.
* Have NRAS mutation.
* Have at least one measurable lesion at baseline per RECIST v1.1
* Eastern Cooperative Oncology Group (ECOG) performance status ≤2
* Age of 19 years or older
* Adequate renal, hematologic and liver function.

Key Exclusion Criteria:

* Have a history of prior treatment with RAF, MEK, or ERK inhibitor.
* Have past history or ongoing retinal pathology that is considered a risk factor for retinopathy or RVO.
* Have past history or ongoing cardiac function-related disorders.
* Had hemorrhage or bleeding corresponding to CTCAE Grade ≥3 within 4 weeks prior to the first dose of study drug treatment (Cycle 1 Day 1).

Where this trial is running

Seongnam-si, Gyeonggi-do and 9 other locations

• Seoul National University Bundang Hospital — Seongnam-si, Gyeonggi-do, South Korea (NOT_YET_RECRUITING)
• Chonnam National University Hwasun Hospital — Hwasun, Jeollanam-do, South Korea (NOT_YET_RECRUITING)
• Dong-A University Medical Center — Busan, South Korea (RECRUITING)
• Kyungpook National University Chilgok Hospital — Daegu, South Korea (NOT_YET_RECRUITING)
• Chungnam National University Hospital — Daejeon, South Korea (NOT_YET_RECRUITING)
• Seoul National University Hospital — Seoul, South Korea (NOT_YET_RECRUITING)
• Severance Hospital — Seoul, South Korea (RECRUITING)
• Asan Medical Center — Seoul, South Korea (RECRUITING)
• Samsung Medical Center — Seoul, South Korea (RECRUITING)
• Korea University Guro Hospital — Seoul, South Korea (NOT_YET_RECRUITING)

Study contacts

• Study coordinator: Young Su (Bobby) Noh

Conditions: Advanced or Metastatic Melanoma, NRAS-Mutant, Melanoma