FDA Grants Breakthrough Designation for SystImmune's Izalontamab Brengitecan in NSCLC

SystImmune and Bristol Myers Squibb's izalontamab brengitecan (iza-bren) has received Breakthrough Therapy Designation from the US FDA for the treatment of locally advanced or metastatic non-small cell lung cancer with EGFR exon 19 deletions or exon 21 L858R substitution mutations who have progressed on EGFR TKI and platinum-based chemotherapy. The designation is based on data from the BL-B01D1-101, BL-B01D1-203, and BL-B01D1-LUNG-101 studies.

SystImmune Inc. and Bristol Myers Squibb (NYSE: BMY) have announced that 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 epidermal growth factor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy [1].

The designation is based on data from the BL-B01D1-101, BL-B01D1-203, and BL-B01D1-LUNG-101 studies. Iza-bren is a potential first-in-class bispecific antibody-drug conjugate (ADC) which targets both epidermal growth factor receptor and human epidermal growth factor receptor 3 (EGFRxHER3) with a topoisomerase 1 inhibitor payload. The granting of Breakthrough Therapy Designation underscores the strength of these data and highlights the potential of iza-bren to address the significant clinical unmet need patients face after EGFR TKI and platinum-based chemotherapy treatment [1].

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. 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 [1].

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. 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 [1].

"[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 is a clinical-stage biopharmaceutical company located in Redmond, WA and Princeton, NJ, specializing in developing innovative cancer treatments using its established drug development platforms, focusing on bi-specific, multi-specific antibodies, and antibody-drug conjugates (ADCs) [1].

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases [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