{"entity":{"id":"bispecific-adc","kind":"technology","name":"Bispecific ADC","aka":[],"tldr":"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.","status":"phase-3","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT06382142: BL-B01D1-307","url":"https://clinicaltrials.gov/study/NCT06382142"},{"label":"ClinicalTrials.gov NCT06304974: PANKU-Esophagus01 (BL-B01D1-305)","url":"https://clinicaltrials.gov/study/NCT06304974"}],"tags":["frontier"],"related":[],"cancers":["tnbc","nsclc","esophageal","urothelial"],"sections":["adcs"],"technologies":["adc","bispecific-antibody"],"targets":["egfr","her3","met","nectin4","trop2","her2","b7h3","pdl1"],"drugs":["izalontamab-brengitecan","tilatamig-samrotecan","ak146d1"],"companies":["systimmune","bms","astrazeneca","akeso","avenzo","valink-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["adc","bispecific-antibody"],"notes":[],"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)","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"],"since":2023},"route":"/technologies/bispecific-adc/","neighbours":{"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"section":[{"id":"adcs","kind":"section","name":"Antibody-Drug Conjugates","route":"/fronts/adcs/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"bispecific-antibody","kind":"technology","name":"Bispecific antibodies","route":"/technologies/bispecific-antibody/"},{"id":"logic-gated-therapeutics","kind":"technology","name":"Logic-gated therapeutics (AND, NOT gates)","route":"/technologies/logic-gated-therapeutics/"}],"target":[{"id":"b7h3","kind":"target","name":"B7-H3","route":"/targets/b7h3/"},{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"her3","kind":"target","name":"HER3","route":"/targets/her3/"},{"id":"met","kind":"target","name":"MET","route":"/targets/met/"},{"id":"nectin4","kind":"target","name":"Nectin-4","route":"/targets/nectin4/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"},{"id":"trop2","kind":"target","name":"TROP2","route":"/targets/trop2/"}],"drug":[{"id":"ak146d1","kind":"drug","name":"AK146D1","route":"/drugs/ak146d1/"},{"id":"izalontamab-brengitecan","kind":"drug","name":"Izalontamab brengitecan","route":"/drugs/izalontamab-brengitecan/"},{"id":"tilatamig-samrotecan","kind":"drug","name":"Tilatamig samrotecan","route":"/drugs/tilatamig-samrotecan/"}],"company":[{"id":"akeso","kind":"company","name":"Akeso","route":"/companies/akeso/"},{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"},{"id":"avenzo","kind":"company","name":"Avenzo Therapeutics","route":"/companies/avenzo/"},{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"},{"id":"pathos-ai","kind":"company","name":"Pathos AI","route":"/companies/pathos-ai/"},{"id":"synaffix","kind":"company","name":"Synaffix (Lonza)","route":"/companies/synaffix/"},{"id":"systimmune","kind":"company","name":"SystImmune / Sichuan Biokin","route":"/companies/systimmune/"},{"id":"valink-therapeutics","kind":"company","name":"Valink Therapeutics","route":"/companies/valink-therapeutics/"}],"trial":[{"id":"nct07591090","kind":"trial","name":"A Phase II Study of AK146D1 Combined With AK112 in Advanced Breast Cancer","route":"/trials/nct07591090/"},{"id":"nct07669779","kind":"trial","name":"A Phase II Study of AK146D1 in Combination With AK112 in Advanced Non-Small Cell Lung Cancer","route":"/trials/nct07669779/"},{"id":"nct06994195","kind":"trial","name":"A Study Comparing BL-B01D1 With the Investigator's Choice of Chemotherapy in Patients With Platinum-resistant Recurrent Epithelial Ovarian Cancer(PANK","route":"/trials/nct06994195/"},{"id":"nct06787664","kind":"trial","name":"A Study of BL-B01D1 in Patients With Locally Advanced or Metastatic Chordoma","route":"/trials/nct06787664/"},{"id":"nct05924841","kind":"trial","name":"A Study of BL-B01D1, SI-B003 and BL-B01D1+SI-B003 in Patients With Extensive Stage Small Cell Lung Cancer","route":"/trials/nct05924841/"},{"id":"nct05990803","kind":"trial","name":"A Study of BL-B01D1, SI-B003 and BL-B01D1+SI-B003 in Patients With Recurrent or Metastatic Cervical Cancer and Other Gynecological Malignancies","route":"/trials/nct05990803/"},{"id":"nct06006169","kind":"trial","name":"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","route":"/trials/nct06006169/"},{"id":"nct06437509","kind":"trial","name":"A Study of BL-B01D1+PD-1 Monoclonal Antibody in Patients With Extensive-stage Small Cell Lung Cancer","route":"/trials/nct06437509/"},{"id":"nct06437522","kind":"trial","name":"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","route":"/trials/nct06437522/"},{"id":"nct05956587","kind":"trial","name":"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","route":"/trials/nct05956587/"},{"id":"nct06008054","kind":"trial","name":"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 ","route":"/trials/nct06008054/"},{"id":"bl-b01d1-307","kind":"trial","name":"BL-B01D1-307","route":"/trials/bl-b01d1-307/"},{"id":"izabright-breast01","kind":"trial","name":"IZABRIGHT-Breast01","route":"/trials/izabright-breast01/"},{"id":"panku-esophagus01","kind":"trial","name":"PANKU-Esophagus01 (BL-B01D1-305)","route":"/trials/panku-esophagus01/"},{"id":"nct07100080","kind":"trial","name":"Study of Izalontamab Brengitecan (BMS-986507) Versus Platinum-Pemetrexed for EGFR-mutated Non-small Cell Lung Cancer After Failure of EGFR TKI Therapy","route":"/trials/nct07100080/"}],"roadmap":[{"id":"adc-generations","kind":"roadmap","name":"ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs","route":"/roadmaps/adc-generations/"},{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"},{"id":"trop2-adc-roadmap","kind":"roadmap","name":"TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET","route":"/roadmaps/trop2-adc-roadmap/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"}],"idea":[{"id":"idea-bio1-dual-antigen-adc-escape","kind":"idea","name":"Two-target antibody drugs to close the antigen escape route","route":"/ideas/idea-bio1-dual-antigen-adc-escape/"}]}}