Dr Levy on Where Iza-Bren May Fit Following Osimertinib In EGFR-Mutated NSCLC

“How [iza-bren] fits in is going to be about the data, not necessarily about the excitement or the putative mechanisms of action of these drugs.”

Benjamin P. Levy, MD, an associate professor of oncology at Johns Hopkins University School of Medicine and clinical director of medical oncology at the Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, discussed the rationale for and emerging data with the EGFR x HER3 bispecific antibody-drug conjugate (ADC) izalontamab brengitecan (iza-bren) in EGFR-mutated non–small cell lung cancer (NSCLC), and where the agent may fit among a growing list of options after progression on osimertinib (Tagrisso).

HER3 expression occurs more commonly in EGFR-mutated lung cancer, making dual targeting rational, Levy explained. He also noted that most data with iza-bren have come from pretreated patients, with competitive response rates and durable responses, although cytopenias remain a challenge.

Levy said the bispecific ADC design is favorable, although he believes a payload other than a topoisomerase I inhibitor could be an improvement. Since most data have come out of China, global data are needed and are now being gathered, he added.

Where iza-bren will fit in the treatment paradigm is unclear given the many agents active after osimertinib, according to Levy, who pointed to the TROP2-directed ADC sacituzumab tirumotecan (sac-TMT; MK-2870), ivonescimab (SMT112) plus carboplatin and pemetrexed which now under FDA review with a target action date of November 14, 2026; and savolitinib for MET-overexpressed or -amplified disease. Whether iza-bren lands in the second line, third line, or front line remains open, he said.

Added that EGFR care has shifted from erlotinib (Tarceva) alone to a multistep patient journey, complicating sequencing for community and academic physicians alike, he concluded.