Toxicities Hinder Potential Efficacy of Ceritinib/Trametinib in Pretreated Advanced Melanoma
Source: OncLive, April 2024
Although dual suppression of the mTOR and MAPK pathways could be a viable therapy avenue for patients with pretreated advanced melanoma, overcoming overlapping toxicities when combining these types of therapies will be paramount, according to Zeynep Eroglu, MD.
A phase 1/2 trial (NCT03501368) evaluated ceritinib (Zykadia) alone and in combination with trametinib (Mekinist) in patients with advanced melanoma that progressed after prior treatment with anti–PD-1 therapy (and prior BRAF/MEK inhibitors, if eligible). Findings presented at the 2024 AACR Annual Meeting showed that no patients treated with single-agent ceritinib (n = 11) responded; 2 patients experienced stable disease (SD). In patients treated with the combination, 2 patients experienced a partial response, and 6 patients had SD.
Notably, dose-limiting toxicities of grade 3 rash and grade 2 glaucoma prompted investigators to de-escalate dosing from dose level 1 of 300 mg of ceritinib per day and 2 mg of trametinib per day to 300 mg and 1.5 mg, respectively. The subsequent dose level was established as the maximum tolerated dose.