Iza-Bren ADC Achieves 100% Response Rate in EGFR-Mutated NSCLC When Combined with Osimertinib
Key Insights
Iza-bren (search), a novel bispecific antibody-drug conjugate targeting EGFR (search) and HER3 (search), demonstrated a 100% objective response rate when combined with osimertinib in first-line EGFR-mutated NSCLC (search) patients.
As monotherapy, iza-bren (search) showed a 66% objective response rate and 12.5-month median progression-free survival in previously treated EGFR-mutated NSCLC (search) patients.
The combination therapy maintained a manageable safety profile with primarily hematologic adverse events, while the 12-month progression-free survival rate reached 92.1%.
A novel bispecific antibody-drug conjugate (ADC) called iza-bren (search) (BL-B01D1) has demonstrated remarkable efficacy in treating EGFR (search)-mutated non-small cell lung cancer (search) (NSCLC (search)), with combination therapy achieving a 100% objective response rate in first-line patients, according to findings presented at the International Association for the Study of Lung Cancer (search) 2025 World Conference on Lung Cancer in Barcelona.
Breakthrough Combination Results
The combination of iza-bren (search) with osimertinib showed unprecedented results in 40 patients with first-line EGFR (search)-mutated locally advanced or metastatic NSCLC (search) treated at the 2.5 mg/kg dose level. The objective response rate (ORR) reached 100%, with a confirmed ORR of 95.0%, where two partial responses are pending confirmation.
"These results are remarkable and suggest that this combination could offer a potentially transformative first-line treatment option for EGFR (search)-mutant NSCLC (search)," said Dr. Fei Zhou from Shanghai East Hospital (search), the study's presenting author. "Importantly, the regimen was also manageable from a safety perspective."
The study enrolled 154 patients who received iza-bren (search) in combination with daily osimertinib at various dose levels: 2.2, 2.5, and 2.75 mg/kg administered on days 1 and 8 every 3-week cycle, and 4.0 and 4.5 mg/kg given on day 1 every 3-week cycle. With a median follow-up of 12.8 months, the 12-month progression-free survival rate in the 2.5 mg/kg cohort reached 92.1%, with median duration of response and progression-free survival not yet reached.
Monotherapy Efficacy Data
Iza-bren (search) also demonstrated significant activity as monotherapy in previously treated patients. Among 171 EGFR-mutated NSCLC (search) patients, a subgroup of 50 patients who had received prior tyrosine kinase inhibitor (TKI) therapy but were chemotherapy-naïve were treated at 2.5 mg/kg on days 1 and 8 every 3-week cycle.
In this population, iza-bren (search) achieved an objective response rate of 66.0% and a confirmed ORR of 56.0%. The median progression-free survival reached 12.5 months, with a median duration of response of 13.7 months. Notably, median overall survival was not reached, with a 12-month overall survival rate of 80.3%.
Novel Mechanism of Action
Iza-bren (search) represents a first-in-class EGFR (search) x HER3 (search) bispecific ADC linked to a novel topoisomerase I (search) inhibitor payload (Ed-04 (search)). This innovative design allows the drug to simultaneously target both EGFR and HER3 receptors while delivering a potent cytotoxic payload directly to cancer cells.
The drug was evaluated across two Phase I/II studies in patients with locally advanced or metastatic solid tumors, with patients receiving various dosing schedules to optimize therapeutic benefit while maintaining safety.
Safety Profile Management
The safety profile of both monotherapy and combination therapy was characterized as manageable by investigators. In the combination study, 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, elevated liver enzymes, hypokalemia, hypoalbuminemia, weight loss, rash, and alopecia.
For monotherapy, the most frequent hematologic TRAEs were anemia (90.6%), leukopenia (80.7%), neutropenia (78.4%), and thrombocytopenia (74.3%). The most common non-hematologic TRAEs included nausea, alopecia, and asthenia. Importantly, only 1.2% of patients discontinued monotherapy due to TRAEs, and no treatment-related deaths were observed.
In the combination therapy, the discontinuation rate due to TRAEs was 13.0%, with grade 3 or higher events manageable through supportive care and dose modifications.
Clinical Development Progress
"This early data suggests iza-bren (search) may offer a promising treatment option for patients with EGFR-mutated NSCLC (search)," said Dr. Wenfeng Fang from Sun Yat-sen University Cancer Center (search) in Guangzhou, China, the lead investigator for the monotherapy study. "Phase III registrational study of iza-bren as monotherapy in EGFR-mutated NSCLC after progression on a third generation TKI is ongoing in China."
The compelling efficacy data from both monotherapy and combination approaches position iza-bren (search) as a potentially transformative treatment option for EGFR-mutated NSCLC (search) patients, addressing a significant unmet medical need in this patient population.