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

NCT07449754 | Recruiting Phase 2 DMC

• 1 other identifier: HM-RAFI-201
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Advanced or Metastatic Melanoma

Keywords

NRAS-Mutant; Melanoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  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 Outcomes (5)

• Disease Control Rate (DCR)

  Throughout the study until disease progression or death whichever occurs first (up to approximately 3 years)

• Duration of response (DOR)

  Throughout the study until disease progression or death whichever occurs first (up to approximately 3 years)

• Progression-free survival (PFS)

  Throughout the study until disease progression or death whichever occurs first (up to approximately 3 years)

• Time to progression (TTP)

  Throughout the study until disease progression (up to approximately 3 years)

• Overall survival (OS)

  Throughout the study until the date of death (up to approximately 3 years)

Study Arms (1)

Belvarafenib + Cobimetinib

EXPERIMENTAL

Belvarafenib in combination with Cobimetinib

Drug: Belvarafenib; Combination Product: Cobimetinib

Interventions

Belvarafenib DRUG

Belvarafenib will be taken twice daily (BID) on Days 1-28 of each cycle

Also known as: HM95573

Belvarafenib + Cobimetinib

Cobimetinib COMBINATION_PRODUCT

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

Also known as: Cotellic

Belvarafenib + Cobimetinib

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Hanmi Pharmaceutical Company Limited: lead

Study Sites (10)

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

NOT YET RECRUITING

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, 58128, South Korea

NOT YET RECRUITING

Dong-A University Medical Center

Busan, 49201, South Korea

RECRUITING

Kyungpook National University Chilgok Hospital

Daegu, 41404, South Korea

NOT YET RECRUITING

Chungnam National University Hospital

Daejeon, 35015, South Korea

NOT YET RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

NOT YET RECRUITING

Severance Hospital

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Korea University Guro Hospital

Seoul, 08308, South Korea

NOT YET RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

cobimetinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Young Su (Bobby) Noh

CONTACT

82-2-410-9277; 63forever@hanmi.co.kr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2026
• First Posted: March 4, 2026
• Study Start: February 12, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): March 1, 2030
• Last Updated: March 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

KR (10)