Kolupin (tunlametinib)

In recent years, MEK inhibitors like binimetinib and tunlametinib have displayed the efficacy for NRASmut melanoma, with tunlametinib being the first and only approved MEK inhibitor for advanced NRASmut melanoma. Subsequently, we explored current and potential treatment approaches for melanoma, primarily encompassing BRAF inhibitors, MEK inhibitors, and immunotherapy, with a particular focus on their clinical relevance of development. Finally, the challenges in the treatment of melanoma, particularly in immunotherapy and targeted therapy, are summarized and discussed.

P4, N=28, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

As of June 2025, the patient has achieved a CR with a progression-free survival of 9 months before experiencing disease recurrence. This rare case of NF1-associated oligodendroglioma was managed with thiotepa, bevacizumab, teniposide, and tunlametinib, highlighting the potential of MEK inhibition in NF1-related gliomas.

P2, N=15, Recruiting, Tianjin Medical University Second Hospital

P2, N=40, Recruiting, Fudan University | Not yet recruiting --> Recruiting

P4, N=5, Not yet recruiting, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Structural elucidation of 12 previously uncharacterized photodegradation impurities was achieved through HPLC/IT-TOF MS. These findings establish a scientific foundation for refining quality specifications of tunlametinib.

P2, N=38, Not yet recruiting, Peking Union Medical College Hospital; Peking Union Medical College Hospital

P2, N=40, Not yet recruiting, Fudan University

In recent years, significant clinical advancements have been achieved by targeting the NRAS-MAPK pathway, with novel therapies such as the MEK inhibitor tunlametinib and the combination therapy of the pan-RAF inhibitor naporafenib with trametinib leading the way. In this review, we will systematically summarize the recent advances in the direct targeting of mutant NRAS proteins and their downstream RAF and MEK proteins, as well as targeting the MAPK pathway in combination with other therapeutic targets, including the immunotherapy, to treat NRAS mutant melanoma. Additionally, we will further discuss the current issues and emerging countermeasures related to targeted therapy for NRAS mutant melanoma.

P3, N=165, Recruiting, Shanghai Kechow Pharma, Inc. | Not yet recruiting --> Recruiting

In March 2024, tunlametinib was granted conditional approval in China (based on surrogate endpoints) for use in patients with NRAS-mutated advanced melanoma who have failed anti-PD-1/PD-L1 treatment. This article summarizes the milestones in the development of tunlametinib leading to this first approval for the treatment of solid tumours with RAS and RAF mutations.