Dr Levy on the Clinical Application of ADCs in NSCLC Following ASCO 2024 Data

Benjamin Levy, MD, clinical director, Medical Oncology, Johns Hopkins Sidney Kimmel Cancer Center, Sibley Memorial Hospital; associate professor, oncology, Johns Hopkins University School of Medicine, and Yan Leyfman, MD, internal medicine and clinical researcher, Mount Sinai; co-founder, executive director, MedNews Week, executive committee member, Music Beats Cancer, discuss the clinical application of antibody-drug conjugates (ADCs) in the treatment of patients with non–small cell lung cancer (NSCLC) on OncLive® News Network: On Location at the 2024 ASCO Annual Meeting.

When asked which ADCs show the most promising potential for clinical applications, Levy states that the 2024 ASCO Annual Meeting appears to be the first ASCO Annual Meeting with so many ADC presentations, reflecting rapid advancements in the field. There are multiple promising options, with findings from the phase 3 EVOKE-01 trial (NCT05089734) taking a prominent place, he says. This study compares sacituzumab govitecan-hziy (Trodelvy) with docetaxel in the second-line setting in an enriched patient population that includes patients with both nonsquamous and squamous disease. Unfortunately, the study did not meet its primary end point of overall survival, but findings from subset analyses will be informative, Levy reports.

The phase 2 TROPION-Lung05 trial (NCT04484142) examined intracranial response rates with single-agent datopotamab deruxtecan (Dato-DXd), a TROP2-directed ADC, in patients with actionable genomic alterations, Levy continues, adding that the study showed an intracranial overall response rate of 22% (95% CI, 6%-48%) in patients with baseline brain metastases, indicating that ADCs can cross the blood-brain barrier.

Another ADC of interest is telisotuzumab vedotin, a MET-directed ADC. Data from the phase 2 LUMINOSITY/M14-239 trial (NCT03539536) were discussed at the meeting, focusing on both patients with EGFR wild-type and EGFR-mutant NSCLC. Preliminary results indicate that patients with wild-type disease with high MET expression derive the most benefit. The nuances of these data will be intriguing to explore, Levy says.

The 2024 ASCO Annual Meeting was incredibly exciting with so much progress seen in the ADC field, especially as advancements in TROP2-directed ADCs, MET-directed ADCs, and translational and predictive biomarkers propel the field forward, according to Levy. This is a thrilling time to witness these developments, he concludes.