Belvarafenib in Combination With Cobimetinib in Patients With Locally Advanced or Metastatic NRAS-Mutant Melanoma

February 27, 2026 updated by: Hanmi Pharmaceutical Company Limited

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 is a Phase 2 open-label, multicenter, single-arm study evaluating the combination of Belvarafenib and Cobimetinib in patients with locally advanced or metastatic melanoma with NRAS mutations. The study plans to assess ORR, DCR, DOR, TTP, PFS, OS and safety of the participating subjects.

Treatment cycles for all subjects will be 28 days in duration and Belvarafenib and Cobimetinib will be administered orally in combination.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

45

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • South Korea
      • Busan, South Korea, 49201
        • Recruiting
        • Dong-A University Medical Center
      • Daegu, South Korea, 41404
        • Not yet recruiting
        • Kyungpook National University Chilgok Hospital
      • Daejeon, South Korea, 35015
        • Not yet recruiting
        • Chungnam National University Hospital
      • Seoul, South Korea, 03080
        • Not yet recruiting
        • Seoul National University Hospital
      • Seoul, South Korea, 05505
        • Recruiting
        • Asan Medical Center
      • Seoul, South Korea, 06351
        • Recruiting
        • Samsung Medical Center
      • Seoul, South Korea, 03722
        • Recruiting
        • Severance Hospital
      • Seoul, South Korea, 08308
        • Not yet recruiting
        • Korea University Guro Hospital
    • Gyeonggi-do
      • Seongnam-si, Gyeonggi-do, South Korea, 13620
        • Not yet recruiting
        • Seoul National University Bundang Hospital
    • Jeollanam-do
      • Hwasun, Jeollanam-do, South Korea, 58128
        • Not yet recruiting
        • Chonnam National University Hwasun Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Belvarafenib + Cobimetinib
Belvarafenib in combination with Cobimetinib
Drug: Belvarafenib
Belvarafenib will be taken twice daily (BID) on Days 1-28 of each cycle
Other Names:
  • HM95573
Combination product: Cobimetinib
Cobimetinib will be taken on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 of each cycle (three times weekly, TIW), followed by a drug holiday through Day 28
Other Names:
  • Cotellic

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR)
Time Frame: Throughout the study until disease progression or death whichever occurs first (up to approximately 3 years)
ORR will be measured as the proportion of subjects with a confirmed response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Independent Central Review (ICR)
Throughout the study until disease progression or death whichever occurs first (up to approximately 3 years)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Control Rate (DCR)
Time Frame: Throughout the study until disease progression or death whichever occurs first (up to approximately 3 years)
DCR will be measured as the proportion of subject with confirmed CR, PR, or Stable Disease (SD) as per RECIST v1.1 by Independent Central Review (ICR)
Throughout the study until disease progression or death whichever occurs first (up to approximately 3 years)
Duration of response (DOR)
Time Frame: Throughout the study until disease progression or death whichever occurs first (up to approximately 3 years)
DOR will be measured as the time from initial onset of CR or PR to first radiographic progression as per RECIST v1.1 by Independent Central Review (ICR) or death from any cause, whichever occurs first.
Throughout the study until disease progression or death whichever occurs first (up to approximately 3 years)
Progression-free survival (PFS)
Time Frame: Throughout the study until disease progression or death whichever occurs first (up to approximately 3 years)
PFS will be measured from date of first treatment until date of radiographic progression as per RECIST v1.1 by Independent Central Review (ICR) or until death from any cause, whichever occurs first
Throughout the study until disease progression or death whichever occurs first (up to approximately 3 years)
Time to progression (TTP)
Time Frame: Throughout the study until disease progression (up to approximately 3 years)
TTI will be measured from date of first treatment until date of rediographic progression as per RECIST v1.1 by Independent Central Review (ICR)
Throughout the study until disease progression (up to approximately 3 years)
Overall survival (OS)
Time Frame: Throughout the study until the date of death (up to approximately 3 years)
OS will be measured from the first administration of the study drug to the date of death due to any cause
Throughout the study until the date of death (up to approximately 3 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hanmi Pharmaceutical Company Limited

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 12, 2026

Primary Completion (Estimated)

September 1, 2029

Study Completion (Estimated)

March 1, 2030

Study Registration Dates

First Submitted

February 27, 2026

First Submitted That Met QC Criteria

February 27, 2026

First Posted (Actual)

March 4, 2026

Study Record Updates

Last Update Posted (Actual)

March 4, 2026

Last Update Submitted That Met QC Criteria

February 27, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HM-RAFI-201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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