{"entity":{"id":"adc-sequencing","kind":"term","name":"ADC sequencing","aka":[],"tldr":"The open question of whether a second ADC works after the first one fails, especially when both carry the same type of payload.","summary":"ADC sequencing is the open question of whether a second antibody-drug conjugate works after the first one fails, especially when both carry the same class of payload. Retrospective series including SATEEN, BRE-354 and data at ESMO Breast 2026 show reduced efficacy when a second TOP1-payload ADC follows immediately after the first; proposed mechanisms are SLFN11 loss, TOP1 mutations, efflux and antigen downregulation. Prospective trials such as TRADE-DXd are under way. The term is attached to Triple-negative breast cancer (TNBC) and HR-positive / HER2-negative breast cancer and to the Antibody-drug conjugate (ADC) technology, and it is referenced by Mersana Therapeutics, the pairing cautioning against TOP1 ADC after TOP1 ADC and the idea of payload-class switching.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate"}],"tags":[],"related":[],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},"route":"/terms/adc-sequencing/","neighbours":{"cancer":[{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"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":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}],"idea":[{"id":"idea-tnbc-adc-sequencing-trial","kind":"idea","name":"A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer","route":"/ideas/idea-tnbc-adc-sequencing-trial/"},{"id":"idea-data-sequencing-analysis-per-approval","kind":"idea","name":"A real-world sequencing analysis within a year of every new approval","route":"/ideas/idea-data-sequencing-analysis-per-approval/"},{"id":"idea-tr2-sequence-registry","kind":"idea","name":"A registry of every treatment sequence patients actually receive, with outcomes","route":"/ideas/idea-tr2-sequence-registry/"},{"id":"idea-tr1-mams-for-sequencing-questions","kind":"idea","name":"Multi-arm, multi-stage trials to answer which order to give approved drugs","route":"/ideas/idea-tr1-mams-for-sequencing-questions/"},{"id":"idea-payload-switching","kind":"idea","name":"Payload-class switching as the rule for ADC sequencing","route":"/ideas/idea-payload-switching/"},{"id":"idea-bio1-pre-randomised-sequencing-trials","kind":"idea","name":"Randomise the next line of treatment before the first one fails","route":"/ideas/idea-bio1-pre-randomised-sequencing-trials/"},{"id":"idea-tr2-pragmatic-sequence-randomisation","kind":"idea","name":"Registry-embedded randomisation of treatment order in routine care","route":"/ideas/idea-tr2-pragmatic-sequence-randomisation/"},{"id":"idea-fra-adc-sequencing-ovarian","kind":"idea","name":"Sequence folate-receptor ADCs by payload class","route":"/ideas/idea-fra-adc-sequencing-ovarian/"},{"id":"idea-her2-adc-sequencing-payload","kind":"idea","name":"Sequencing HER2 ADCs by payload after T-DXd","route":"/ideas/idea-her2-adc-sequencing-payload/"},{"id":"idea-tr2-smart-sequencing-adc","kind":"idea","name":"Sequential multiple-assignment randomised trials to find the best order of ADCs","route":"/ideas/idea-tr2-smart-sequencing-adc/"},{"id":"idea-bio1-slfn11-payload-guidance","kind":"idea","name":"Use SLFN11 status to decide which antibody-drug payload to give next","route":"/ideas/idea-bio1-slfn11-payload-guidance/"}],"paper":[{"id":"paper-tropion-breast02-ann-oncol-2026","kind":"paper","name":"Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial","route":"/key-papers/paper-tropion-breast02-ann-oncol-2026/"},{"id":"paper-destiny-breast03-nejm-2022","kind":"paper","name":"DESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer","route":"/key-papers/paper-destiny-breast03-nejm-2022/"},{"id":"paper-tropion-breast01-jco-2024","kind":"paper","name":"TROPION-Breast01: datopotamab deruxtecan versus chemotherapy in pretreated hormone-receptor-positive breast cancer, and why a PFS win did not translate to survival","route":"/key-papers/paper-tropion-breast01-jco-2024/"}],"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/"}],"company":[{"id":"mersana","kind":"company","name":"Mersana Therapeutics","route":"/companies/mersana/"}],"pairing":[{"id":"adc-after-adc-caution","kind":"pairing","name":"Caution: TOP1 ADC immediately after TOP1 ADC","route":"/pairings/adc-after-adc-caution/"}],"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/"}],"term":[{"id":"cross-resistance","kind":"term","name":"Cross-resistance","route":"/terms/cross-resistance/"},{"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/"}],"pathway":[{"id":"drug-efflux-pumps","kind":"pathway","name":"Drug efflux pumps (ABC transporters)","route":"/pathways/drug-efflux-pumps/"}]}}