PAK4 Inhibition Increases Anti-PD-1 Response in Mouse Models Prompting Phase I Trial

Source: GenomeWeb, January 2020

NEW YORK – A new study has identified an apparent role for the PAK4 oncogene in anti-PD-1 checkpoint immunotherapy, prompting a Phase I clinical trial of a PAK4 inhibitor in combination with the PD-1 targeting drug nivolumab (Opdivo from Bristol-Myers Squibb) in around 175 individuals with advanced solid tumors or non-Hodgkin’s lymphoma.

The Karyopharm Therapeutics-sponsored trial kicked off in the spring of 2016 and is expected to run until next spring at several sites in the US and Canada, according to available information on ClinicalTrials.gov. It involves a Karyopharm Therapeutics drug candidate known as KPT-9274 that targets both PAK4 and the nicotinamide phosphoribosyl-transferase (NAMPT) enzyme.

In the current study, published online today in Nature Cancer, researchers from the University of California at Los Angeles, Karyopharm Therapeutics, and elsewhere did RNA sequencing on dozens of individuals with melanoma, searching for gene expression features that coincided with enhanced or diminished immune T cell infiltration of tumors in samples collected before and during PD-1 blockage treatment.