Kolupin (tunlametinib) / KeChow Pharma - LARVOL DELTA

Multimodal treatment with thiotepa, bevacizumab, teniposide, and tunlametinib in a patient with neurofibromatosis type 1-associated oligodendroglioma: a rare case report. (PubMed, Anticancer Drugs) - "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."

Journal • Brain Cancer • Genetic Disorders • Glioma • Neurofibromatosis • Oligodendroglioma • Oncology • Solid Tumor • NF1

Phase II Trial of Tunlametinib in Patients With NRAS Mutant Non-melanoma Refractory Solid Tumors (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: Tianjin Medical University Second Hospital

New P2 trial • Non-melanoma Skin Cancer • Oncology • Solid Tumor

A prospective, single-arm, open-label exploratory clinical study evaluating the efficacy and safety of the combination therapy of toramatinib, vemurafenib and cetuximab in the first-line treatment of unresectable or advanced BRAF V600E mutant colorectal cancer (ChiCTR) - P4 | N=5 | Not yet recruiting | Sponsor: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

New P4 trial • Colorectal Cancer • Oncology • Solid Tumor • BRAF

IIT-085-TC-002: Phase II Trial of Tunlametinib in NRAS-Mutant Advanced Thyroid Cancer (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Fudan University | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Characterization of 12 Unknown Photodegradation Impurities of Tunlametinib Capsules Using Liquid Chromatography Coupled With ion Trap/Time-Of-Flight Mass Spectrometry. (PubMed, Rapid Commun Mass Spectrom) - "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."

IO biomarker • Journal • Melanoma • Neuroblastoma • Oncology • Solid Tumor • NRAS

A Study Evaluating the Efficacy and Safety of Torametinib (HL085) in Combination with Fruquintinib and Hydroxychloroquine (HCQ) in Patients with RAS/BRAFV600E Mutation-Positive Refractory Advanced Colorectal Cancer (ChiCTR) - P2 | N=38 | Not yet recruiting | Sponsor: Peking Union Medical College Hospital; Peking Union Medical College Hospital

New P2 trial • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • BRAF • KRAS • NRAS

Novel Therapies for Neurofibromatosis Type 1-Associated Inoperable Plexiform Neurofibromas: A Systematic Literature Review (ISPOR 2025) - "These reported on a total of 21 unique studies on 11 emerging therapies: 6 MEK inhibitors (selumetinib, mirdametinib, trametinib, binimetinib, FCN-159, tunlametinib) and 5 targeted anti-cancer agents (cabozantinib, tipifarnib, sorafenib, sirolimus, everolimus)... The promising results of MEK inhibitors in therapeutic trials for NF1 demonstrate that targeting the MAPK/ERK pathway is an attractive therapeutic avenue for unresectable PNs. Because selumetinib is only approved for children, future reimbursement will require advanced studies establishing MEK inhibitor efficacy in adults."

Review • Brain Cancer • Genetic Disorders • Neurofibromatosis • Oncology • Solid Tumor • NF1

Targeting the MAPK Pathway for NRAS Mutant Melanoma: From Mechanism to Clinic. (PubMed, Br J Dermatol) - "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."

IO biomarker • Journal • Melanoma • Oncology • Solid Tumor • NRAS

An Exploratory Clinical Study Evaluating the Efficacy and Safety of Tunlametinib Combined With Fruquintinib in the Third-line Treatment of Advanced Colorectal Cancer Patients With RAS Mutations. (clinicaltrials.gov) - P=N/A | N=34 | Not yet recruiting | Sponsor: Liu Huang

New trial • Colorectal Cancer • Oncology • Solid Tumor

IIT-085-TC-002: A Prospective, Single-Arm, Open-Label, Single-Center Phase II Exploratory Clinical Study to Evaluate the Efficacy and Safety of Tunlametinib in Subjects With NRAS-Mutant Locally Advanced or Metastatic Thyroid Cancer (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Fudan University

New P2 trial • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma

Efficacy and Safety of Tunlametinib Plus Vemurafenib in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer (clinicaltrials.gov) - P3 | N=165 | Recruiting | Sponsor: Shanghai Kechow Pharma, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Oncology • Solid Tumor • BRAF

Tunlametinib: First Approval. (PubMed, Drugs) - "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."

IO biomarker • Journal • Review • Colorectal Cancer • Gastrointestinal Cancer • Genetic Disorders • Lung Cancer • Melanoma • Neurofibromatosis • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MAP2K1 • NF1 • NRAS

Comparing Tunlametinib Capsules and Combination Chemotherapy in Advanced NRAS-mutant Melanoma (clinicaltrials.gov) - P3 | N=165 | Recruiting | Sponsor: Shanghai Kechow Pharma, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • IO biomarker • Metastases • Melanoma • Oncology • Solid Tumor • NRAS

Tunlametinib (HL-085) plus vemurafenib in patients with advanced BRAF V600-mutant solid tumors: an open-label, single-arm, multicenter, phase I study. (PubMed, Exp Hematol Oncol) - P1 | "Tunlametinib (HL-085) plus vemurafenib had a favorable safety profile and showed promising antitumor activity in patients with BRAF V600-mutant solid tumors. The RP2D for NSCLC was tunlametinib 9 mg BID plus vemurafeinib 720 mg BID."

Journal • Metastases • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Hematological Disorders • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

A phase II study of tunlametinib in combination with vemurafenib in patients with BRAF V600-mutant advanced melanoma. (ASCO 2024) - P1, P2 | "The addition of a MEK inhibitor tunlametinib to vemurafenibexhibited promising clinical efficacy in Chinese patients with BRAF V600-mutant advanced melanoma, with a manageable safety profile. Additionally, notable effects were observed in pts with acral melanoma. The efficacy in pre-treated patients was comparable to that of similar agents in previous untreated patients."

Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • BRAF

A phase III, open-label, multicenter, randomized controlled trial of tunlametinib versus investigator-selected chemotherapy in patients with advanced NRAS-mutant melanoma who had previously received immunotherapy. (ASCO 2024) - P3 | "Control group subjects will receive one of the following regimens which according to investigator's choice (paclitaxel plus carboplatin, or temozolomide plus cisplatin, or dacarbazine plus cisplatin) , 28 days per cycle. Exploratory endpoints are to evaluate quality of life between two groups and to development a companion diagnostic kit for NRAS gene mutations detection. This study is currently open for enrollment."

Clinical • IO biomarker • IO Companion diagnostic • Metastases • P3 data • Melanoma • Oncology • Solid Tumor • NRAS

Overall survival and efficacy subgroup analysis of tunlametinib in patients with advanced NRAS-mutant melanoma: A multicenter, open-label, single-arm, phase 2 study. (ASCO 2024) - P2 | "Tunlametinib demonstrated an encouraging treatment response rate in patients with advanced NRAS-mutant melanoma with a manageable safety profile. These results suggest that tunlametinib could be a promising treatment option for NRAS-mutant melanoma, even for those who had previously received immunotherapy."

Clinical • IO biomarker • Metastases • P2 data • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • NRAS

KeChow Pharma Announces NMPA Approval of Tunlametinib (HL-085) as the First Targeted Therapy for Patients with NRAS Mutated Advanced Melanoma and Previously Treated with PD-1/PD-L1 (PRNewswire) - "KeChow Pharma...announced that the China National Medical Products Administration (NMPA) has approved tunlametinib (HL-085) for the treatment of patients with NRAS mutated advanced melanoma who were previously treated with PD-1/PD-L1....The new drug application (NDA) of tunlametinib was previously granted priority review by the Center for Drug Evaluation (CDE) of the NMPA. The approval was based on the results of a multicenter, single-arm, phase II, pivotal registrational study which conducted in 100 patients in China (NCT05217303)."

Non-US regulatory • Melanoma

A phase II study of efficacy and safety of the MEK inhibitor tunlametinib in patients with advanced NRAS-mutant melanoma (Eur J Cancer) - P2 | N=100 | NCT05217303 | Sponsor: Shanghai Kechow Pharma, Inc. | "All (n = 100) patients received at least one dose of tunlametinib (safety analysis set [SAS]) and 95 had central laboratory-confirmed NRAS mutations (full analysis set [FAS]). In the FAS, NRAS mutations were observed at Q61 (78.9%), G12 (15.8%) and G13 (5.3%). The IRRC-assessed ORR was 35.8%, with a median DOR of 6.1 months. The median PFS was 4.2 months, DCR was 72.6% and median OS was 13.7 months. Subgroup analysis showed that in patients who had previously received immunotherapy, the ORR was 40.6%. No treatment-related deaths occurred."

P2 data • Melanoma

A phase II study of efficacy and safety of the MEK inhibitor tunlametinib in patients with advanced NRAS-mutant melanoma. (PubMed, Eur J Cancer) - P2 | "Tunlametinib showed promising antitumor activity with a manageable safety profile in patients with advanced NRAS-mutant melanoma, including those who had prior exposure to immunotherapy. The findings warrant further validation in a randomized clinical trial."

Clinical • IO biomarker • Journal • Metastases • P2 data • Melanoma • Oncology • Solid Tumor • NRAS

Efficacy and safety of tunlametinib (HL-085) combined with vemurafenib in patients with advanced BRAF V600-mutated solid tumors: A multicenter, phase I study (ESMO 2023) - P1 | "Conclusions Tunlametinib in combination with vemurafenib showed promising antitumor activity and manageable safety profile in pts with BRAF V600-mutated solid tumors. Further studies are ongoing."

Clinical • Metastases • P1 data • Colorectal Cancer • Endocrine Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • BRAF

Preclinical characterization of tunlametinib, a novel, potent, and selective MEK inhibitor. (PubMed, Front Pharmacol) - " In vitro, tunlametinib demonstrated high selectivity with approximately 19-fold greater potency against MEK kinase than MEK162, and nearly 10-100-fold greater potency against RAS/RAF mutant cell lines than AZD6244...Furthermore, tunlametinib combined with BRAF/KRAS/SHP2 inhibitors or docetaxel showed synergistically enhanced response and marked tumor inhibition. Tunlametinib exhibited a promising approach for treating RAS/RAF mutant cancers alone or as combination therapies, supporting the evaluation in clinical trials. Currently, the first-in-human phase 1 study and pivotal clinical trial of tunlametinib as monotherapy have been completed and pivotal trials as combination therapy are ongoing."

Journal • Preclinical • Oncology • KRAS

Comparing Tunlametinib Capsules and Combination Chemotherapy in Advanced NRAS-mutant Melanoma (clinicaltrials.gov) - P3 | N=165 | Not yet recruiting | Sponsor: Shanghai Kechow Pharma, Inc.

IO biomarker • Metastases • New P3 trial • Melanoma • Oncology • Solid Tumor • NRAS

Preclinical characterization of tunlametinib, a novel, potent, and selective MEK inhibitor (Front Pharmacol) - "In vitro, tunlametinib demonstrated high selectivity with approximately 19-fold greater potency against MEK kinase than MEK162, and nearly 10–100-fold greater potency against RAS/RAF mutant cell lines than AZD6244. In vivo, tunlametinib resulted in dramatic tumor suppression and profound inhibition of ERK phosphorylation in tumor tissue."

Preclinical • Oncology

Efficacy and Safety of Tunlametinib Plus Vemurafenib in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer (clinicaltrials.gov) - P3 | N=165 | Not yet recruiting | Sponsor: Shanghai Kechow Pharma, Inc.

Metastases • New P3 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF