FDA Grants Breakthrough Therapy Designation to Iza-Bren for Non-Small Cell Lung Cancer Treatment

SystImmune and Bristol Myers Squibb have announced that the FDA has granted Breakthrough Therapy Designation to izalontamab brengitecan (iza-bren) for treating locally advanced or metastatic non-small cell lung cancer with specific mutations that have progressed on EGFR tyrosine kinase inhibitors and platinum-based chemotherapy. The designation was based on data from three ongoing trials conducted in China and globally.

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to izalontamab brengitecan (iza-bren) for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with specific mutations that have progressed on EGFR tyrosine kinase inhibitors (TKIs) and platinum-based chemotherapy. The designation was based on data from three ongoing trials conducted in China and globally [1].

Izalontamab brengitecan is a potential first-in-class bispecific antibody-drug conjugate (ADC) that targets both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3) with a topoisomerase 1 inhibitor payload. It is being developed by Biokin in China and jointly developed by SystImmune and Bristol Myers Squibb under a collaboration and exclusive license agreement in territories outside of China [1].

The FDA's decision underscores the potential of iza-bren to address a significant clinical unmet need in patient care. While EGFR TKIs have shown clinical efficacy in the frontline setting, most patients eventually see their cancer progress after about 18 months. Subsequent treatment options often contain platinum-based chemotherapy, which are of limited efficacy and come with significant toxicities [1].

Breakthrough Therapy Designation from the US FDA is intended to expedite the development and review of drugs that may demonstrate significant benefit over current standards of care. The FDA's decision was based on efficacy and safety data from three ongoing clinical trials: BL-B01D1-101 and BL-B01D1-203, conducted in China by Sichuan Biokin Pharmaceutical Co., Ltd., and the global BL-B01D1-LUNG-101 study conducted by SystImmune across the United States, Europe, and Japan [1].

Across these trials, iza-bren demonstrated evidence to suggest improved efficacy with a manageable safety profile in patients with EGFR-mutant NSCLC who had progressed after third-generation EGFR TKIs and platinum-based chemotherapy. "The FDA's granting of Breakthrough Therapy Designation underscores the potential of iza-bren to meaningfully improve clinical outcomes for patients with previously treated epidermal growth factor receptor mutation NSCLC," said Dr. Jonathan Cheng, Chief Medical Officer of SystImmune [1].

SystImmune, a clinical-stage biopharmaceutical company, and Bristol Myers Squibb (NYSE: BMY) are collaborating to develop iza-bren. SystImmune specializes in developing innovative cancer treatments using its established drug development platforms, focusing on bi-specific, multi-specific antibodies, and antibody-drug conjugates (ADCs) [1].

References:
[1] https://www.morningstar.com/news/pr-newswire/20250818sf52891/izalontamab-brengitecan-egfrxher3-adc-granted-breakthrough-therapy-designation-by-us-fda-for-patients-with-previously-treated-advanced-egfr-mutated-non-small-cell-lung-cancer