A combination of iza-bren (BL-B01D1), a novel bispecific antibody-drug conjugate (ADC), with osimertinib demonstrated a 100% objective response rate (ORR) in patients with first-line EGFR-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC).

This study was presented at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer (WCLC).

Iza-bren is a first-in-class ADC combining EGFR and HER3 targeting with a topoisomerase I inhibitor payload. The study tested iza-bren at multiple dose levels in combination with daily osimertinib, a third-generation EGFR tyrosine kinase inhibitor. Among 40 patients treated at 2.5 mg/kg, the ORR was 100% and the confirmed ORR (cORR) was 95.0%, with two partial responses pending confirmation.

“These results are remarkable and suggest that this combination could offer a potentially transformative first-line treatment option for EGFR-mutant NSCLC,” said Dr. Fei Zhou, presenting author from Shanghai East Hospital. “Importantly, the regimen was also manageable from a safety perspective.”

Dr. Zhou and his colleagues enrolled 154 patients who received iza-bren in combination with osimertinib at 2.2, 2.5, 2.75 mg/kg D1D8 Q3W (Day 1 and Day 8 every 3-week cycle) and 4.0, 4.5 mg/kg D1 Q3W (Day 1 every 3-week cycle).

The median follow-up was 12.8 months. In the 2.5 mg/kg cohort (n=40), the ORR was 100% and the 12-month progression-free survival rate was 92.1%. Dr. Zhou noted that the median duration of response (DOR) and PFS had not yet been reached.

Most treatment-related adverse events (TRAEs) were hematologic, including anemia (91.9%), neutropenia (91.1%), leukopenia (91.1%), and thrombocytopenia (75.6%). Non-hematologic TRAEs included nausea, stomatitis, decreased appetite, vomiting, diarrhea, asthenia, AST increased, ALT increased, hypokalemia, hypoalbuminemia, weight decreased, rash and alopecia. Grade 3 or higher events were manageable with supportive care and dose modifications. The discontinuation rate of iza-bren due to TRAEs was 13.0%.

“Iza-bren in combination with osimertinib has demonstrated promising activity with a manageable safety profile in first-line EGFR-mutated NSCLC patients,” Dr. Zhou reported.

Provided by
International Association for the Study of Lung Cancer