Bispecific ADC
A bispecific ADC is an ADC whose antibody grabs two different proteins on the cancer cell, so it sticks better to tumour and less to healthy tissue.
Izalontamab brengitecan (iza-bren, EGFR×HER3, SystImmune/BMS) is the first bispecific ADC with positive phase 3 results, meeting PFS and OS in previously treated TNBC (BL-B01D1-307, February 2026) and in oesophageal cancer, with first-line trials (IZABRIGHT-Breast01) ongoing. Eight bsADC phase 3 trials started in 2025. c-MET×EGFR is the most crowded pair (tilatamig samrotecan, AZD9592, 24 candidates); Nectin-4×TROP2 (AK146D1, AVZO-103), HER2 biparatopic (zanidatamab zovodotin), and PD-L1×B7-H3 (BH4601) follow.
How it works
Dual antigen binding increases avidity and internalisation and can enable lysosomal trafficking (e.g., pairing with a rapidly internalising receptor). Biparatopic designs cross-link one receptor.
- Better tumour selectivity and internalisation
- Addresses heterogeneity: cells expressing either antigen are hit
- Can deliver higher DAR safely
- Complex CMC
- Two-target biology harder to predict
- Toxicity still payload-driven
AK146D1 is Akeso's Nectin-4 × TROP2 bispecific ADC, combining the two most validated ADC addresses in one molecule.
Izalontamab brengitecan is the first bispecific ADC to succeed in a phase 3 trial, hitting two growth receptors at once in triple-negative breast cancer.
AstraZeneca's EGFR×c-MET bispecific ADC, the most advanced in the most crowded next-generation ADC target pair.
Latest papers
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