Bristol Myers Squibb's Izalontamab Brengitecan Receives FDA Breakthrough Therapy Designation for Advanced NSCLC

The FDA has granted Breakthrough Therapy Designation to izalontamab brengitecan (iza-bren) for advanced EGFR-mutated non-small cell lung cancer. The designation is based on promising data from three clinical trials. Bristol Myers Squibb and SystImmune aim to expedite development and review for this potential first-in-class therapy. Iza-bren targets both EGFR and HER3 receptors and addresses the need for more effective treatments in cases where current therapies typically meet resistance after 18 months.

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to izalontamab brengitecan (iza-bren), a potential first-in-class bispecific antibody-drug conjugate (ADC) for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations. The designation is based on promising data from three clinical trials [1].

Iza-bren, developed by Biokin in China and jointly developed by SystImmune and Bristol Myers Squibb, targets both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3) with a topoisomerase 1 inhibitor payload. The FDA's decision underscores the potential of iza-bren to address the significant clinical unmet need patients face after EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy treatment [2].

Breakthrough Therapy Designation from the 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 [3].

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. Iza-bren offers a novel approach by blocking EGFR and HER3 signals to cancer cells and causing genotoxic stress, potentially improving clinical outcomes for patients with previously treated EGFR-mutated NSCLC [4].

References:
[1] https://www.marketscreener.com/news/izalontamab-brengitecan-egfrxher3-adc-granted-breakthrough-therapy-designation-by-u-s-fda-for-pat-ce7c51dcd98efe27
[2] https://www.onclive.com/view/fda-grants-breakthrough-therapy-designation-to-izalontamab-brengitecan-in-egfr-nsclc
[3] 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