Top Targets and Novel Biomarkers Attract Interest in NSCLC

Liza C. Villaruz, MD, associate professor of medicine and co-leader of the Immunotherapy and Drug Development Center at UPMC Hillman Cancer Center, discusses the most promising biomarkers in the non–small cell lung cancer (NSCLC) space.

She says that the known driver mutations in oncogenes have been most successful, such as EGFR, ALK, ROS1, and RET. There are approved targeted therapies for these alterations that are effective enough to be used as frontline therapy for patients with NSCLC, making broad genetic testing important for patients with advanced disease.

PD-L1 is also an important biomarker since PD-L1 expression level is predictive of benefit in patients who receive immune checkpoint inhibitors alone or in combination with other therapies. This includes pembrolizumab (Keytruda) monotherapy and combination nivolumab (Opdivo) plus ipilimumab (Yervoy), which targets both PD-1 and CTLA-4.

In terms of upcoming therapy targets, Villaruz says research will show whether TROP expression is predictive of response to TROP2 inhibitors such as the antibody-drug conjugate (ADC) datopotamab deruxtecan; if so, this will be another valuable biomarker. The adhesion molecule CEACAM5 is another biomarker with a novel therapy tusamitamab ravtansine (SAR408701) under investigation in the phase 2 CARMEN-LC05 trial (NCT04524689). Additionally, MET may become a more significant biomarker, as research into c-MET ADCs including telisotuzumab vedotin has shown potential for patients with MET alterations.

TRANSCRIPTION:

0:08 | We have our oncogene driven disease, and they are the gold standard in terms of predictive biomarkers of therapeutic benefit with regard to EGFR, ALK, ROS1, and RET. We have PD-L1, which is the gold standard for predicting therapeutic benefits to immunotherapy, either by itself, chemoimmunotherapy combinations, or immunotherapy/immunotherapy combinations—combined PD-1 and CTLA-4 therapies.

I think as we go forward, [it will] be interesting to see how TROP…is predictive of benefit to TROP2 inhibitors, and also CEACAM5, because there are novel therapies aimed toward that as well. I think it'll be interesting to see how all of these different biomarkers could potentially predict the benefit of their targeted agents. There is still a fair amount of work with MET, and several different MET ADCs, which are also within development.