SystImmune and Bristol Myers Squibb developed and commercialized izalontamab brengitecan (iza-bren [BL-B01D1]), a bispecific ADC that targets both EGFR and HER3. The therapy is already making waves in multiple Phase III trials across China, and now it is diving into the first-line NSCLC setting. The Phase I data of the therapy is with a cut-off date of December 5, 2024 iza-bren showed promising activity with a manageable safety profile and good efficacy.

The most common hematologic TRAEs were anemia (87.7%), leukopenia (74.0%), thrombocytopenia (74.0%), and neutropenia (72.6%). Non-hematologic TRAEs included asthenia (42.5%), nausea (41.1%), stomatitis (37.0%), diarrhea (32.9%), and alopecia (31.5%). Grade ≥3 TRAEs were mostly hematologic and manageable with supportive care. Discontinuation due to TRAEs was low (2.7%). One case of grade 2 ILD was reported, with no treatment-related deaths or new safety signals observed.

KOL insights

“Recent data have bolstered our confidence in iza-bren's safety profile while highlighting its encouraging efficacy across tumors that have been difficult to treat. Iza-bren emerges as a promising therapeutic option, potentially fulfilling the unmet need of patients with few treatment alternatives. Our commitment to advancing this therapy through a series of comprehensive clinical trials remains steadfast, as we explore its potential both as a standalone treatment and in combination with other agents to improve cancer patient outcomes globally. ” – Expert Opinion.

Conclusion

In 2024, the total incident cases of NSCLC in the United States was ~204,820. The treatment landscape for EXON-20 mutant NSCLC has been evolving, with RYBREVANT (developed by Johnson & Johnson) and EXKIVITY (Takeda) previously being the approved therapies in this niche market. EXON-20 mutant NSCLC, which represents 10–12% of EGFR mutant NSCLC cases, has historically been an underserved segment with limited treatment options, making it an unproven market with a small patient base. However, in 2023, EXKIVITY was withdrawn from the market, leaving RYBREVANT as the sole approved therapy for this specific mutation. Key players looking to enter in the EXON-20 market include EQRx International/Hansoh Pharmaceutical, Merus/Betta Pharmaceuticals, Taiho Oncology, Dizal Pharmaceuticals, and others. 

In the highly competitive NSCLC landscape, where multiple targeted therapies already exist for mutations such as HER2, ALK, ROS1, RET fusions, KRAS, BRAF, MET fusions, and SMARCA4, SystImmune’s iza-bren will face significant market pressure. To differentiate itself and capture meaningful market share, iza-bren must demonstrate not just promising activity but clear advantages—such as superior progression-free survival (PFS), overall survival (OS), or improved safety—over both established and emerging treatments. Only through compelling clinical outcomes can iza-bren position itself as a standout option in this increasingly crowded therapeutic space.