{"entity":{"id":"idea-post-neoadjuvant-adc","kind":"idea","name":"ADC for residual disease after KEYNOTE-522","aka":[],"tldr":"Patients whose TNBC survives chemo-immunotherapy before surgery have a high relapse risk. Give them an ADC after surgery.","summary":"Patients whose TNBC survives neoadjuvant chemo-immunotherapy carry a high relapse risk, and this idea gives them a TROP2 ADC, with or without pembrolizumab, after surgery. It applies the KATHERINE model, T-DM1 for HER2-positive residual disease, to TNBC with residual cancer burden after KEYNOTE-522 therapy. Residual disease is chemoresistant but not necessarily ADC-resistant, because the payload is delivered at concentrations chemotherapy cannot reach. The concept is being tested at scale in ASCENT-05 with sacituzumab govitecan plus pembrolizumab and in TROPION-Breast03 with datopotamab deruxtecan, and ctDNA-defined high-risk subgroups should be pre-specified. It forms part of the TNBC roadmap.","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT03036488: KEYNOTE-522","url":"https://clinicaltrials.gov/study/NCT03036488"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["adc"],"targets":[],"drugs":["sacituzumab-govitecan","datopotamab-deruxtecan","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["rcb","pcr"],"trials":["keynote-522"],"people":[],"bottlenecks":[],"keyPapers":["paper-keynote-522-n-engl-j-med-2020","paper-keynote-355-lancet-2020","paper-ascent-nejm-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adjuvant TROP2 ADC ± pembrolizumab improves iDFS in TNBC with residual disease (RCB I-III) after neoadjuvant KEYNOTE-522 therapy compared with pembrolizumab ± capecitabine.","rationale":"Residual disease is chemoresistant but not necessarily ADC-resistant; ADC payload is delivered at concentrations chemotherapy cannot reach.","test":"ASCENT-05 and TROPION-Breast03 readouts expected 2026-27; ctDNA-defined high-risk subgroups should be pre-specified.","maturity":"being-tested-at-scale"},"route":"/ideas/idea-post-neoadjuvant-adc/","neighbours":{"cancer":[{"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/"}],"drug":[{"id":"datopotamab-deruxtecan","kind":"drug","name":"Datopotamab deruxtecan","route":"/drugs/datopotamab-deruxtecan/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"}],"term":[{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"},{"id":"rcb","kind":"term","name":"Residual cancer burden (RCB)","route":"/terms/rcb/"}],"trial":[{"id":"ascent-05","kind":"trial","name":"ASCENT-05 / OptimICE-RD (AFT-65, GBG 119, NSABP B-63)","route":"/trials/ascent-05/"},{"id":"keynote-522","kind":"trial","name":"KEYNOTE-522","route":"/trials/keynote-522/"},{"id":"tropion-breast03","kind":"trial","name":"TROPION-Breast03","route":"/trials/tropion-breast03/"}],"paper":[{"id":"paper-ascent-nejm-2021","kind":"paper","name":"ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer","route":"/key-papers/paper-ascent-nejm-2021/"},{"id":"paper-katherine-nejm-2019","kind":"paper","name":"KATHERINE: switching to T-DM1 when HER2-positive breast cancer survives pre-surgery treatment","route":"/key-papers/paper-katherine-nejm-2019/"},{"id":"paper-keynote-522-nejm-2022","kind":"paper","name":"KEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancer","route":"/key-papers/paper-keynote-522-nejm-2022/"},{"id":"paper-keynote-522-n-engl-j-med-2020","kind":"paper","name":"Pembrolizumab for Early Triple-Negative Breast Cancer","route":"/key-papers/paper-keynote-522-n-engl-j-med-2020/"},{"id":"paper-keynote-355-lancet-2020","kind":"paper","name":"Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial","route":"/key-papers/paper-keynote-355-lancet-2020/"}],"roadmap":[{"id":"tnbc-history","kind":"roadmap","name":"TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line","route":"/roadmaps/tnbc-history/"}]}}