Promising Results for Novel Antibody-Drug Conjugate in EGFR-Mutated Non-Small Cell Lung Cancer

A new antibody-drug conjugate (ADC), named iza-bren (BL-B01D1), has demonstrated encouraging safety and effectiveness in treating patients with EGFR-mutated non-small cell lung cancer (NSCLC), according to findings unveiled at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer. Iza-bren is a pioneering EGFR x HER3 bispecific ADC that delivers a novel topoisomerase I inhibitor payload (Ed-04). It was evaluated through two Phase I/II clinical trials involving patients with advanced or metastatic solid tumors, including those with EGFR mutations. Patients were administered various doses and schedules, such as day one and day eight every three weeks (D1D8 Q3W) and day one every three weeks (D1 Q3W). In a subgroup of 50 patients who had prior TKI treatment and were chemo-naive, receiving 2.5 mg/kg D1D8 Q3W, the objective response rate (ORR) reached 66.0%, with a confirmed ORR (cORR) of 56.0%. The median progression-free survival (mPFS) was 12.5 months, the median duration of response (mDOR) was 13.7 months, and the median overall survival (mOS) was not reached, with a 12-month OS rate of 80.3%. Lead investigator Dr. Wenfeng Fang from Sun Yat-sen University Cancer Center in Guangzhou, China, highlighted that the safety profile was manageable. The most common hematologic treatment-related adverse events (TRAEs) included anemia (90.6%), leukopenia (80.7%), neutropenia (78.4%), and thrombocytopenia (74.3%). Non-hematologic TRAEs such as nausea, hair loss, and weakness were also observed, but only 1.2% of patients discontinued treatment due to adverse effects, and no treatment-related deaths occurred. Dr. Fang expressed optimism, stating that early data indicates iza-bren could be a promising therapeutic option for patients with EGFR-mutated NSCLC. An ongoing Phase III clinical trial in China is further exploring iza-bren as a monotherapy for this patient population after progression on third-generation TKIs. This research signifies an important step forward in targeted lung cancer therapies, offering new hope for improved outcomes.