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.
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.
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.
P1, N=27, Not yet recruiting, Shanghai Kechow Pharma, Inc. | Trial completion date: Aug 2021 --> Dec 2022 | Trial primary completion date: Aug 2020 --> Dec 2022
over 3 years ago
Clinical • Trial completion date • Trial primary completion date
Our data demonstrated that HL-085 is well tolerated, with manageable side-effects and promising anti-cancer activity in pts with NRASm advanced melanoma. Research Funding: Shanghai KeChow Pharma