The following is a summary of “Combination of PAC-1 and entrectinib for the treatment of metastatic uveal melanoma,” published in the December 2023 issue of Dermatology by Boudreau, et al.
The treatment of metastatic uveal melanoma continued to be a significant issue in the clinical setting. The procaspase-3 protein, which is a proapoptotic protein and a precursor to the important apoptotic executioner caspase-3, is overexpressed in a broad variety of cancers. The medicine PAC-1 takes advantage of this overexpression to destroy cancer cells selectively. For a study, researchers sought to present the results of their investigation into the effectiveness of PAC-1 against uveal melanoma cell lines, as well as the synergistic combination of PAC-1 with entrectinib.
A modest Phase 1b trial was conducted on patients who had metastatic uveal melanoma. The study was conducted because of the preclinical activity of these medications and the proven clinical efficacy of these treatments in human cancer patients. The administration of PAC-1 and entrectinib together was well tolerated by these individuals, and there were no treatment-related toxicities of grade ≥3 that were observed. The administration of PAC-1 did not have any consequences on the pharmacokinetics of entrectinib.
Stable disease was reported in four out of six patients in this first cohort that was quite small and had received extensive pretreatment. The median progression-free survival was 3.38 months, with a 95% CI ranging from 1.6 to 6.5 months. As a preliminary demonstration, this research demonstrates that the combination of PAC-1 and entrectinib may be worthy of future clinical exploration because of its potential benefits.
