Dr Levy on Onco-Directed ADCs in NSCLC

Benjamin Philip Levy, MD, clinical director, Medical Oncology, associate professor, oncology, Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, discusses antibody-drug conjugates (ADCs) under investigation in patients with non–small cell lung cancer (NSCLC), which he presented on at the 18th Annual New York Lung Cancers Symposium^®.

As ADCs gain prominence in the NSCLC treatment field, some may be categorized as onco-directed agents, meaning they may be particularly effective in patients with certain driver alterations, Levy says. At the New York Lung Cancers Symposium, Levy’s presentation focused on ADCs with activity in patients with EGFR-mutant, HER2-positive, and MET overexpressed disease. Previously at the 2023 IASLC World Conference on Lung Cancer, data from the phase 2 DESTINY-Lung02 trial (NCT04644237) were presented. In the trial, patients with pretreated, metastatic NSCLC with HER2 exon 20 insertion mutations who received the ADC fam-trastuzumab deruxtecan-nxki (Enhertu) at 5.4 mg/kg and 6.4 mg/kg achieved confirmed overall response rates (ORRs) of 49.0% (95% CI, 39.0%-59.1%) and 56.0% (95% CI, 41.3%-70.0%), respectively.

Regarding patritumab deruxtecan, the phase 2 HERTHENA-Lung01 trial (NCT04619004) showed that the ADC elicited a confirmed ORR of 29.8% (95% CI, 23.9%-36.2%) in patients with EGFR-mutated NSCLC who had previously received an EGFR TKI and platinum-based chemotherapy, and it generated a confirmed ORR of 29.2% (95% CI, 23.1%-35.9%) in a subset of patients who had received prior third-generation EGFR TKIs and platinum-based chemotherapy.

Furthermore, the MET-directed ADC telisotuzumab vedotin (ABBV-399) is being investigated in a phase 2 trial (NCT03539536) in patients with previously treated, MET-overexpressed NSCLC. Although MET overexpression often occurs in patients without EGFRmutations, it can also occur in patients with EGFR-mutated disease that has become resistant to prior TKIs, Levy notes. The goal of this New York Lung Cancers Symposium presentation was to contextualize the available data with ADCs in NSCLC and lay the framework for future investigations in this arena, Levy concludes.