{"entity":{"id":"izalontamab-brengitecan","kind":"drug","name":"Izalontamab brengitecan","aka":[],"tldr":"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.","summary":"EGFR×HER3 bispecific ADC from SystImmune (Sichuan Biokin), partnered with Bristol Myers Squibb (2023, up to $8.4B). Phase 3 BL-B01D1-307 in previously treated locally advanced/metastatic TNBC met PFS and OS at interim analysis (announced 26 February 2026; presented ASCO 2026). Also positive in oesophageal squamous cell carcinoma. IZABRIGHT-Breast01 (first-line TNBC, PD-1 ineligible) and trials in NSCLC (EGFR-mutant, post-TKI), urothelial, nasopharyngeal, and SCLC are ongoing. Haematologic toxicity is the main limitation.","status":"phase-3","asOf":"2026-09-04","links":[{"label":"OncLive report","url":"https://www.onclive.com/view/iza-bren-yields-pfs-and-os-benefits-vs-chemo-in-previously-treated-advanced-tnbc"}],"tags":[],"related":[],"cancers":["tnbc","esophageal","nsclc","urothelial"],"sections":[],"technologies":["bispecific-adc","adc"],"targets":["egfr","her3"],"drugs":[],"companies":["systimmune","bms"],"institutions":[],"pathways":[],"terms":["hydrophilic-next-gen"],"trials":["bl-b01d1-307","izabright-breast01","nct06838273","nct07502300","nct06382129","nct07640789","nct06994195","nct06118333","nct07642024","nct07100080","nct06500026","nct06382116","nct06475300","nct06498986","nct06437522","nct07054567","nct05880706","nct05956587","nct05990803","nct06006169","nct05924841","nct06008054","nct06437509","nct06787664"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"iza-bren, BL-B01D1","modality":"Bispecific ADC","payload":"Ed-04 (camptothecin-derived TOP1 inhibitor), DAR ~8","linker":"Cleavable","mechanism":"Dual EGFR/HER3 binding drives internalisation across heterogeneous tumours; TOP1 payload with bystander effect.","approvals":[],"mechanismSteps":["Antibody binds EGFR and HER3 (bispecific) on the tumour cell surface","Receptor-ADC complex is internalised by endocytosis","Trafficked to the lysosome; linker is cleaved or antibody degraded","Ed-04 (camptothecin-derived TOP1 inhibitor) is released inside the cell","Topoisomerase-I is trapped on DNA; replication forks collapse into double-strand breaks","Tumour cell dies by apoptosis","Membrane-permeable payload diffuses to kill neighbouring antigen-negative cells (bystander effect)"],"dosing":{"route":"IV infusion","schedule":"2.5 mg/kg on days 1 and 8 of each 21-day cycle (phase 3 TNBC regimen)","monitoring":"Blood counts (neutropenia, anaemia, thrombocytopenia), stomatitis, ILD symptoms","source":"https://clinicaltrials.gov/study/NCT06382142"},"toxicity":[{"event":"Neutropenia","note":"Haematologic toxicity is the main limitation in phase 1-3 reports; rates per ASCO 2026 presentation"},{"event":"Anaemia"},{"event":"Thrombocytopenia"},{"event":"Stomatitis"},{"event":"Nausea"}],"access":[{"country":"US","reimbursement":"Investigational; BMS filing expected after BL-B01D1-307","asOf":"2026-09-06"},{"country":"CN","reimbursement":"NMPA filings under review (2026)","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2023-12-11","type":"filing","region":"US","note":"BMS licenses global rights ex-China from SystImmune (up to $8.4B)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2026-02-26","type":"filing","region":"China","note":"Positive interim phase 3 in pretreated TNBC (BL-B01D1-307) announced; regulatory submissions follow","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}]},"route":"/drugs/izalontamab-brengitecan/","neighbours":{"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"egfr-mutant-nsclc","kind":"cancer","name":"EGFR-mutated non-small-cell lung cancer","route":"/cancers/egfr-mutant-nsclc/"},{"id":"tnbc-metastatic","kind":"cancer","name":"Metastatic triple-negative breast cancer","route":"/cancers/tnbc-metastatic/"},{"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/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"bispecific-adc","kind":"technology","name":"Bispecific ADC","route":"/technologies/bispecific-adc/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"her3","kind":"target","name":"HER3","route":"/targets/her3/"}],"company":[{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"},{"id":"systimmune","kind":"company","name":"SystImmune / Sichuan Biokin","route":"/companies/systimmune/"}],"term":[{"id":"exatecan","kind":"term","name":"Exatecan (and derivatives)","route":"/terms/exatecan/"},{"id":"hydrophilic-next-gen","kind":"term","name":"Hydrophilic next-generation linkers (TMALIN, Dolaflexin, sulfonyl-pyrimidine, PEG-containing)","route":"/terms/hydrophilic-next-gen/"},{"id":"topoisomerase-i-payloads","kind":"term","name":"Topoisomerase-I inhibitor payloads","route":"/terms/topoisomerase-i-payloads/"}],"trial":[{"id":"nct07502300","kind":"trial","name":"A Study Comparing BL-B01D1 Combined With Tislelizumab Versus Platinum-containing Chemotherapy Combined With Tislelizumab as First-line Treatment in Pa","route":"/trials/nct07502300/"},{"id":"nct07640789","kind":"trial","name":"A Study Comparing BL-B01D1 in Combination With Osimertinib Versus Osimertinib Alone in Patients With Locally Advanced, Unresectable EGFR-mutated Non-s","route":"/trials/nct07640789/"},{"id":"nct07739199","kind":"trial","name":"A Study Comparing BL-B01D1 in Combination With PD-1/VEGF Bispecific Antibody Versus Chemotherapy in Combination With PD-1/VEGF Bispecific Antibody in First-line","route":"/trials/nct07739199/"},{"id":"nct06382129","kind":"trial","name":"A Study Comparing BL-B01D1 With Docetaxel in Patients With Unresectable Locally Advanced or Metastatic EGFR Wild-type Non-small Cell Lung Cancer(PANKU","route":"/trials/nct06382129/"},{"id":"nct06118333","kind":"trial","name":"A Study Comparing BL-B01D1 With Physician's Choice of Chemotherapy in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma(PANKU-NPC01)","route":"/trials/nct06118333/"},{"id":"nct06382116","kind":"trial","name":"A Study Comparing BL-B01D1 With Platinum Based Chemotherapy in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer(PANKU-Lung01)","route":"/trials/nct06382116/"},{"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":"nct06500026","kind":"trial","name":"A Study Comparing BL-B01D1 With Topotecan in Patients With Recurrent Small Cell Lung Cancer(PANKU-Lung03)","route":"/trials/nct06500026/"},{"id":"nct07739186","kind":"trial","name":"A Study Evaluating BL-B01D1 in Combination With a PD-1/VEGF Bispecific Antibody Versus Tislelizumab Plus Platinum-doublet Chemotherapy as First-line Treatment f","route":"/trials/nct07739186/"},{"id":"nct07054567","kind":"trial","name":"A Study of BL-B01D1 + Pembrolizumab ± Bevacizumab in Patients With Recurrent or Metastatic Cervical Cancer and Endometrial Cancer","route":"/trials/nct07054567/"},{"id":"nct05880706","kind":"trial","name":"A Study of BL-B01D1 and BL-B01D1 in Combination With Osimertinib Mesylate Tablets in Patients With Locally Advanced or Metastatic Non-small Cell Lung ","route":"/trials/nct05880706/"},{"id":"nct07827261","kind":"trial","name":"A Study of BL-B01D1 Combined With Glecirasib in Patients With KRAS G12C-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer","route":"/trials/nct07827261/"},{"id":"nct07642024","kind":"trial","name":"A Study of BL-B01D1 in Combination With Osimertinib as Perioperative Therapy in Patients With EGFR-mutated Resectable Non-small Cell Lung Cancer(PANKU","route":"/trials/nct07642024/"},{"id":"nct06498986","kind":"trial","name":"A Study of BL-B01D1 in Combination With Osimertinib Mesylate Tablets in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer","route":"/trials/nct06498986/"},{"id":"nct06838273","kind":"trial","name":"A Study of BL-B01D1 in Combination With Osimertinib Versus Osimertinib as First-Line Treatment in Patients With EGFR-Mutated Locally Advanced or Metas","route":"/trials/nct06838273/"},{"id":"nct06787664","kind":"trial","name":"A Study of BL-B01D1 in Patients With Locally Advanced or Metastatic Chordoma","route":"/trials/nct06787664/"},{"id":"nct07729956","kind":"trial","name":"A Study of BL-B01D1 Plus an Anti-PD-1 Antibody Versus Nab-paclitaxel Plus an Anti-PD-1 Antibody in Patients With Previously Untreated, Locally Advanced, Inopera","route":"/trials/nct07729956/"},{"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":"nct06475300","kind":"trial","name":"A Study of BL-B01D1+PD-1 Monoclonal Antibody in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer, Nasopharyngeal Carcinoma and ","route":"/trials/nct06475300/"},{"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":"nct07825753","kind":"trial","name":"Protein-Matched ADC or PDC Umbrella Trial in Advanced Pancreatic and Breast Cancer","route":"/trials/nct07825753/"},{"id":"nct07680790","kind":"trial","name":"Study of Izalontamab Brengitecan (BMS-986507) in Combination With Osimertinib Versus Osimertinib Monotherapy or Osimertinib in Combination With Platinum-based C","route":"/trials/nct07680790/"},{"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/"}],"institution":[{"id":"sysucc","kind":"institution","name":"Sun Yat-sen University Cancer Center","route":"/institutions/sysucc/"}],"pairing":[{"id":"tki-then-adc-lung","kind":"pairing","name":"EGFR TKI → ADC on 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