Iza-Bren in combination with Osimertinib Shows 100% Response Rate in EGFR-Mutated NSCLC, Phase II Study Finds
Barcelona, Spain (September, 2025) —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 today 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 has not yet 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.
About the IASLC:
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated solely to the study of lung cancer and other thoracic malignancies. Founded in 1974, the association's membership includes more than 10,000 lung cancer specialists across all disciplines in over 100 countries, forming a global network working together to conquer lung and thoracic cancers worldwide. The association also publishes the Journal of Thoracic Oncology, the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies. Visit www.iaslc.org for more information.
About the WCLC:
The WCLC is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting nearly 7,000 researchers, physicians, and specialists from more than 100 countries. The goal is to increase awareness, collaboration and understanding of lung cancer, and to help participants implement the latest developments across the globe. The conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For more information, visit https://wclc.iaslc.org/.