{"entity":{"id":"dual-payload-adc","kind":"technology","name":"Dual-payload ADC","aka":[],"tldr":"A dual-payload ADC is an ADC carrying two different poisons at once, so the tumour cannot escape by becoming resistant to one.","summary":"Programs from Sutro, Mersana, Tavotek/Adcoris (ACR335, TOP1 inhibitor + non-TOP1/non-tubulin, DAR 4+4, phase 1 in 2026), and others place two payloads with distinct mechanisms on one antibody. Rationale: TOP1-payload cross-resistance after T-DXd, sacituzumab, or Dato-DXd. Also 'dual-mechanism' ADCs pairing a cytotoxic with an immune agonist.","status":"phase-1","asOf":"2026-09-04","links":[{"label":"Yamazaki et al., Antibody-drug conjugates with dual payloads for combating breast tumour heterogeneity and drug resistance (Nature Communications 2021)","url":"https://doi.org/10.1038/s41467-021-23793-7"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["adcs"],"technologies":["adc","site-specific-conjugation"],"targets":[],"drugs":[],"companies":["callio-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-yamazaki-nat-commun"],"journals":[],"dependsOn":[],"notes":[],"principle":"Orthogonal site-specific conjugation chemistries attach two payload classes at defined positions.","generation":"4th (next-gen)","strengths":["Delays resistance","Combination therapy without additive antibody dose"],"limitations":["Manufacturing","Two toxicity profiles in one molecule"]},"route":"/technologies/dual-payload-adc/","neighbours":{"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":"site-specific-conjugation","kind":"technology","name":"Site-specific conjugation & linker chemistry","route":"/technologies/site-specific-conjugation/"}],"company":[{"id":"callio-therapeutics","kind":"company","name":"Callio Therapeutics","route":"/companies/callio-therapeutics/"},{"id":"debiopharm","kind":"company","name":"Debiopharm","route":"/companies/debiopharm/"},{"id":"sutro-biopharma","kind":"company","name":"Sutro Biopharma","route":"/companies/sutro-biopharma/"}],"paper":[{"id":"paper-yamazaki-nat-commun","kind":"paper","name":"Antibody-drug conjugates with dual payloads for combating breast tumor heterogeneity and drug resistance","route":"/key-papers/paper-yamazaki-nat-commun/"}],"cancer":[{"id":"tnbc-metastatic","kind":"cancer","name":"Metastatic triple-negative breast cancer","route":"/cancers/tnbc-metastatic/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"roadmap":[{"id":"adc-generations","kind":"roadmap","name":"ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs","route":"/roadmaps/adc-generations/"},{"id":"tnbc-history","kind":"roadmap","name":"TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line","route":"/roadmaps/tnbc-history/"},{"id":"trop2-adc-roadmap","kind":"roadmap","name":"TROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET","route":"/roadmaps/trop2-adc-roadmap/"}],"idea":[{"id":"idea-dual-payload-first","kind":"idea","name":"Dual-payload ADCs in first line to prevent resistance","route":"/ideas/idea-dual-payload-first/"},{"id":"idea-payload-switching","kind":"idea","name":"Payload-class switching as the rule for ADC sequencing","route":"/ideas/idea-payload-switching/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-combination-space","kind":"bottleneck","name":"Too many combinations to test","route":"/bottlenecks/b-combination-space/"}]}}