NCT07170293

Phase II Trial of Tunlametinib in Patients With NRAS Mutant Non-melanoma Refractory Solid Tumors

An Exploratory, Prospective, Single Arm, Open Label, Single Center, Basket, Phase II Clinical Study of Tunlametinib (HL-085) in Patients With NRAS Mutant Non-melanoma Refractory Solid Tumors

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: Tianjin Medical University Second Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study is a single cohort, open label exploratory clinical trial aimed at observing and evaluating the efficacy and safety of Tunlametinib (HL-085) in the treatment of refractory solid tumors with advanced metastatic non melanoma. It is expected that the ORR of Tunlametinib (HL-085) treatment can reach 20%. According to the literature results, the experimental group rate is 0.2 and the target value rate is 0.02. If the bilateral alpha is 0.05 and the beta is 0.2, the sample size is calculated as 12 cases in the experimental group. Considering a 20% dropout rate, a total of 15 cases are required.

Detailed description

Members of the RAS gene family, including KRAS, NRAS, and HRAS, can participate in promoting cell metabolism, proliferation, survival, growth, and angiogenesis through the PIK3CA/AKT and RAS/RAF/MAPK signaling pathways downstream of the EGFR tyrosine kinase receptor. Mutations in these genes can lead to sustained activation of downstream signaling pathways, resulting in abnormal cell proliferation and differentiation, which is closely related to the occurrence and development of cancer. The frequency of NRAS gene changes (including CNV and SNV variations) in 10000 patients with advanced metastatic tumors included in the MSK-IMPACT cohort was approximately 3%, with melanoma, thyroid cancer, thymic tumor, primary lesion unknown cancer, and colorectal cancer ranking among the top 5 cancers. At the same time, a large number of domestic studies have shown that the frequency of NRAS gene changes (including CNV and SNV variations) is about 2%, among which the top 5 cancers are melanoma, thyroid cancer, gastrointestinal neuroendocrine tumors, endometrial cancer, and primary lesion unknown cancer. This study is an open exploratory clinical trial aimed at observing and evaluating the efficacy and safety of Tunlametinib in the treatment of non-melanoma refractory solid tumors with NRAS mutations.

Conditions

• Solid Cancers

Interventions

Type	Name	Description
DRUG	Tunlametinib	Do not chew, dissolve or open the capsule. If you miss a dose of medication, you can take the missed dose 8 hours before the next dose. If the time until the next medication is less than 8 hours, it is not recommended to take it again. Every 21 days for one cycle, subjects will use the investigational drug until the treatment termination criteria specified in the protocol are met. The recommended dosage for the first dose reduction is 9mg, twice daily. The recommended second dose reduction is 6mg, twice daily.

Timeline

• Start date: 2027-08-31
• Primary completion: 2027-09-30
• Completion: 2027-09-30
• First posted: 2025-09-12
• Last updated: 2025-09-12

Locations

1 site across 1 country: China