Poster Presentation Australasian Melanoma Conference 2026

Phase 2, multicenter, single-arm study of belvarafenib in combination with cobimetinib in patients with locally advanced or metastatic neuroblastoma-RAS mutant melanoma   (#416)

Sang Joon Shin 1 , Jeeyun Lee 2 , Jeonghwan Youk 3 , Hye Ryeon Kim 4 , Soo Jung Lee 5 , Hyo-Jin Lee 6 , Yong Sang Hong 7 , Hyun-Jung Shim 8 , Eun Joo Kang 9 , Koung Jin Suh 10 , Seong-jung Kim 11 , Sooa Jung 11 , Heera Roh 11 , Munjoo Cho 11 , Eu-Kyung Jo 11 , Eunhye Baek 11 , Taewan Kim 11 , Jiyeon Yoon 11 , Young Su Noh 11
  1. Division of Medical Oncology, Department of Internal Medicine, Yonsei College of Medicine, Seoul, Republic of Korea
  2. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Republic of Korea
  3. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
  4. Division of Hematology-Oncology, Department of Internal Medicine, Dong-A University College of Medicine, Busan, Republic of Korea
  5. Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea
  6. Division of Hemato-Oncology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea
  7. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
  8. Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Republic of Korea
  9. Division of Hematology-Oncology, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea
  10. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
  11. Department of ONCO Clinical Research and Development, Hanmi Pharmaceutical. Co., Ltd., Seoul, Republic of Korea

Background

The MAPK signaling pathway regulates key cellular processes, including proliferation, differentiation, and survival. Although targeting the MAPK pathway with RAF and MEK inhibitors have demonstrated clinical benefits, responses are often limited by adaptive bypass signaling and acquired resistance, including RAF dimerization, leading to limited durability. Belvarafenib is a RAF dimer inhibitor designed to overcome resistance driven by RAF dimerization. In combination with the MEK inhibitor cobimetinib, this approach aims to achieve more comprehensive inhibition of MAPK signaling and suppress compensatory pathway activation. Preliminary anti-tumor activity of belvarafenib in combination with cobimetinib has been observed in an early-phase study (NCT03284502). This phase II study aims to further evaluate the efficacy and durability of this combination in patients with NRAS- mutant melanoma (NCT07449754).

 

Method

This is a multicenter, single-arm, open-label, phase II study evaluating belvarafenib in combination with cobimetinib in patients with locally advanced or metastatic NRAS-mutant melanoma. Approximately 45 patients will be enrolled, with central confirmation of NRAS mutation. Patients will receive belvarafenib 300 mg twice daily continuously (Days 1-28) and cobimetinib 20mg three times weekly (Days 1-21) followed by a 7-day drug holiday, in a 28-day cycle. The primary endpoint is objective response rate. Secondary endpoints include disease control rate, duration of response, time to progression, progression-free survival, overall survival, and safety. Exploratory endpoints include pharmacokinetics and pharmacodynamics. Tumor responses will be assessed per RECIST v1.1, primarily by investigator, but endpoints will be assessed based on independent central review outcomes. The first patient was enrolled in February 2026, and the study is currently ongoing.

 

Result

Not applicable (Trial in progress)