CDK7 inhibition, a new strategy discussed during ESMO

CDK7 is a key kinase regulating cell cycle, transcription of oncogenic and anti-apoptotic genes and ligand-independent expression of genes responsive to hormone receptors: that’s why it’s now being evaluated as a possible target for new antitumor drugs. Samuraciclib, an oral selective CDK7 inhibitor, is the first in its class to be evaluated in a first-in-human trial and results of two studies have been presented during the last ESMO congress.
For the first trial, presented by Matthew Krebs of Experimental Cancer Medicine Team – The Christie NHS Foundation Trust di Manchester, tolerability, pharmacodynamics and efficacy of samuraciclib have been evaluated; results have clearly shown that the drug has a good safety profile and also that food has no clinically significant effect on exposure, while 360 mg once daily could be the preliminary recommended phase II dose. 82% of 44 patients recruited were evaluable for response and 53% evidenced disease control; 12 patients with triple negative breast cancer had stable disease at first post baseline scan and 3 patients have been on treatment longer than one year. Promising data came from a second first-in-human trial coordinated by the same research group: samuraciclib has been tested in combination with fulvestrant in patients with advanced HER2- breast cancer previously treated with an aromatase inhibitor and a CDK4/6 inhibitor. The combination treatment was generally well tolerated and the majority of patients stayed on treatment until disease progression; one patient with partial response has been in treatment for almost one year. This study confirms an acceptable safety profile with evidence of antitumor activity for samuraciclib