Dr. Bazhenova on a Correlative Analysis of the KRYSTAL-1 Trial in Advanced NSCLC

Lyudmila A. Bazhenova, MD, medical oncologist and professor of clinical medicine at the University of California, San Diego, discusses the results of a preliminary exploratory correlative analysis of the phase 1/2 KRYSTAL-1 trial in advanced non–small cell lung cancer (NSCLC).

During the 2021 European Lung Cancer Virtual Congress, additional findings from the KRYSTAL-1 trial were presented, including a preliminary analysis of co-mutations with KRAS G12C and response rates in patients with NSCLC who were treated with adagrasib. Notably, a 64% overall response rate (ORR) was observed in patients who harbored KRAS G12C and STK11 mutations. Comparatively, the ORR was 33% in patients with STK11 wild-type disease and 45% for the overall patient population treated with adagrasib. No correlation was observed between response rate and the presence of KEAP1, TP53, or other common mutations.

These findings signify that additional data are needed to glean why patients with STK11 mutations appear to derive additional benefit from adagrasib, says Bazhenova. Moreover, it is possible that combining adagrasib with pembrolizumab (Keytruda) could leverage the tumor’s natural response to upregulate PD-L1 in an inflamed microenvironment, concludes Bazhenova.