{"entity":{"id":"tilatamig-samrotecan","kind":"drug","name":"Tilatamig samrotecan","aka":[],"tldr":"AstraZeneca's EGFR×c-MET bispecific ADC, the most advanced in the most crowded next-generation ADC target pair.","summary":"Tilatamig samrotecan is AstraZeneca's bispecific antibody-drug conjugate that binds both EGFR and c-MET and delivers the topoisomerase I inhibitor AZ14170133 through a cleavable linker. Its low-affinity EGFR arm and high-affinity c-MET arm mean avidity biases delivery toward tumour cells co-expressing both receptors and spares normal tissue that expresses EGFR alone. It is in phase 2 in EGFR-mutant NSCLC after osimertinib and in EGFR-wild-type NSCLC, per AstraZeneca's 2026 pipeline, and is also being explored in head and neck cancer. Stomatitis, nausea, fatigue and neutropenia are the reported toxicities, and dose optimisation on an every-3-weeks schedule is under way. It is the most advanced of roughly 24 c-MET×EGFR ADC candidates, so its results will shape a crowded field. It is a two-address ADC meant to hit lung cancers carrying both EGFR and c-MET while sparing normal cells.","status":"phase-2","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov: trials of Tilatamig samrotecan","url":"https://clinicaltrials.gov/search?intr=AZD9592"}],"tags":[],"related":[],"cancers":["nsclc","head-and-neck"],"sections":[],"technologies":["bispecific-adc"],"targets":["egfr","met"],"drugs":[],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":["nct05647122"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"AZD9592","modality":"Bispecific ADC","payload":"AZ14170133 (TOP1 inhibitor)","linker":"Cleavable","mechanism":"Bispecific EGFR/c-MET IgG with TOP1 payload; avidity-driven tumour selectivity.","approvals":[],"mechanismSteps":["Antibody binds EGFR and c-MET (bispecific) on the tumour cell surface","Receptor-ADC complex is internalised by endocytosis","Trafficked to the lysosome; linker is cleaved or antibody degraded","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":"Phase 2 dose-optimisation; every 3 weeks","source":"https://clinicaltrials.gov/study/NCT05647122"},"toxicity":[{"event":"Stomatitis"},{"event":"Nausea"},{"event":"Fatigue"},{"event":"Neutropenia"}],"access":[{"country":"US","reimbursement":"Investigational","asOf":"2026-09-06"}],"regulatoryEvents":[]},"route":"/drugs/tilatamig-samrotecan/","neighbours":{"cancer":[{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"bispecific-adc","kind":"technology","name":"Bispecific ADC","route":"/technologies/bispecific-adc/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"met","kind":"target","name":"MET","route":"/targets/met/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"trial":[{"id":"nct05647122","kind":"trial","name":"First in Human Study of AZD9592 in Solid Tumors","route":"/trials/nct05647122/"}],"roadmap":[{"id":"adc-generations","kind":"roadmap","name":"ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs","route":"/roadmaps/adc-generations/"}],"term":[{"id":"exatecan","kind":"term","name":"Exatecan (and derivatives)","route":"/terms/exatecan/"},{"id":"topoisomerase-i-payloads","kind":"term","name":"Topoisomerase-I inhibitor payloads","route":"/terms/topoisomerase-i-payloads/"}]}}