# Bispecific ADC

Source: https://onco.cc/technologies/bispecific-adc/  
OnCo record `bispecific-adc` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Technology
- Status: phase-3
- Last checked: 2026-09-04
- Tags: frontier
- Principle: 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.
- Generation: 4th (next-gen)
- Since: 2023
- Strengths: Better tumour selectivity and internalisation; Addresses heterogeneity: cells expressing either antigen are hit; Can deliver higher DAR safely
- Limitations: Complex CMC; Two-target biology harder to predict; Toxicity still payload-driven

## Sources

- ClinicalTrials.gov NCT06382142: BL-B01D1-307: https://clinicaltrials.gov/study/NCT06382142
- ClinicalTrials.gov NCT06304974: PANKU-Esophagus01 (BL-B01D1-305): https://clinicaltrials.gov/study/NCT06304974

## Connected records

- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- fronts: [Antibody-Drug Conjugates](https://onco.cc/fronts/adcs/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Bispecific antibodies](https://onco.cc/technologies/bispecific-antibody/), [Logic-gated therapeutics (AND, NOT gates)](https://onco.cc/technologies/logic-gated-therapeutics/)
- targets: [B7-H3](https://onco.cc/targets/b7h3/), [EGFR](https://onco.cc/targets/egfr/), [HER2](https://onco.cc/targets/her2/), [HER3](https://onco.cc/targets/her3/), [MET](https://onco.cc/targets/met/), [Nectin-4](https://onco.cc/targets/nectin4/), [PD-L1](https://onco.cc/targets/pdl1/), [TROP2](https://onco.cc/targets/trop2/)
- drugs: [AK146D1](https://onco.cc/drugs/ak146d1/), [Izalontamab brengitecan](https://onco.cc/drugs/izalontamab-brengitecan/), [Tilatamig samrotecan](https://onco.cc/drugs/tilatamig-samrotecan/)
- companies: [Akeso](https://onco.cc/companies/akeso/), [AstraZeneca](https://onco.cc/companies/astrazeneca/), [Avenzo Therapeutics](https://onco.cc/companies/avenzo/), [Bristol Myers Squibb](https://onco.cc/companies/bms/), [Pathos AI](https://onco.cc/companies/pathos-ai/), [Synaffix (Lonza)](https://onco.cc/companies/synaffix/), [SystImmune / Sichuan Biokin](https://onco.cc/companies/systimmune/), [Valink Therapeutics](https://onco.cc/companies/valink-therapeutics/)
- trials: [A Phase II Study of AK146D1 Combined With AK112 in Advanced Breast Cancer](https://onco.cc/trials/nct07591090/), [A Phase II Study of AK146D1 in Combination With AK112 in Advanced Non-Small Cell Lung Cancer](https://onco.cc/trials/nct07669779/), [A Study Comparing BL-B01D1 With the Investigator's Choice of Chemotherapy in Patients With Platinum-resistant Recurrent Epithelial Ovarian Cancer(PANK](https://onco.cc/trials/nct06994195/), [A Study of BL-B01D1 in Patients With Locally Advanced or Metastatic Chordoma](https://onco.cc/trials/nct06787664/), [A Study of BL-B01D1, SI-B003 and BL-B01D1+SI-B003 in Patients With Extensive Stage Small Cell Lung Cancer](https://onco.cc/trials/nct05924841/), [A Study of BL-B01D1, SI-B003 and BL-B01D1+SI-B003 in Patients With Recurrent or Metastatic Cervical Cancer and Other Gynecological Malignancies](https://onco.cc/trials/nct05990803/), [A Study of BL-B01D1, SI-B003 and BL-B01D1+SI-B003 in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma and Other Solid Tumor](https://onco.cc/trials/nct06006169/), [A Study of BL-B01D1+PD-1 Monoclonal Antibody in Patients With Extensive-stage Small Cell Lung Cancer](https://onco.cc/trials/nct06437509/), [A Study of BL-B01D1+PD-1 Monoclonal Antibody in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma and Other Solid Tumors](https://onco.cc/trials/nct06437522/), [A Study of SI-B003 and BL-B01D1+SI-B003 in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer, Nasopharyngeal Carcinoma and Other](https://onco.cc/trials/nct05956587/), [A Study of SI-B003, BL-B01D1+SI-B003 and BL-B01D1+PD-1 Monoclonal Antibody in Patients With Locally Advanced or Metastatic Esophageal Cancer, Gastric ](https://onco.cc/trials/nct06008054/), [BL-B01D1-307](https://onco.cc/trials/bl-b01d1-307/), [IZABRIGHT-Breast01](https://onco.cc/trials/izabright-breast01/), [PANKU-Esophagus01 (BL-B01D1-305)](https://onco.cc/trials/panku-esophagus01/), [Study of Izalontamab Brengitecan (BMS-986507) Versus Platinum-Pemetrexed for EGFR-mutated Non-small Cell Lung Cancer After Failure of EGFR TKI Therapy](https://onco.cc/trials/nct07100080/)
- roadmaps: [ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs](https://onco.cc/roadmaps/adc-generations/), [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/), [TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET](https://onco.cc/roadmaps/trop2-adc-roadmap/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/)
- ideas: [Two-target antibody drugs to close the antigen escape route](https://onco.cc/ideas/idea-bio1-dual-antigen-adc-escape/)

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