{"entity":{"id":"idea-neoadjuvant-adc-io","kind":"idea","name":"Neoadjuvant ADC + IO replacing anthracycline chemotherapy in TNBC","aka":[],"tldr":"Replace the toughest part of pre-surgery chemotherapy with an ADC plus immunotherapy, aiming for the same cure rate with less harm.","summary":"This idea replaces the anthracycline part of pre-surgery chemotherapy in TNBC with a TROP2 ADC plus pembrolizumab, aiming for the same cure rate with less harm. The KEYNOTE-522 backbone carries cardiac and leukaemia risk from anthracyclines, while ADCs deliver the same chemotherapy class more selectively and ADC-induced immunogenic death complements checkpoint blockade. Sacituzumab govitecan and datopotamab deruxtecan with pembrolizumab already show activity in metastatic disease and in the NeoSTAR and I-SPY 2 arms. The test is a randomised phase 3 against the KEYNOTE-522 regimen with pathologic complete response and then event-free survival endpoints. At early-clinical maturity it bears on the ADC plus checkpoint inhibitor pairing and the SCARLET trial.","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT03036488: KEYNOTE-522","url":"https://clinicaltrials.gov/study/NCT03036488"},{"label":"ClinicalTrials.gov NCT05929768: SCARLET (SWOG S2212)","url":"https://clinicaltrials.gov/study/NCT05929768"}],"tags":[],"related":["adc-plus-io"],"cancers":["tnbc"],"sections":[],"technologies":["adc","checkpoint-inhibitor"],"targets":[],"drugs":["sacituzumab-govitecan","datopotamab-deruxtecan","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-522","scarlet-s2212"],"people":[],"bottlenecks":[],"keyPapers":["paper-keynote-522-n-engl-j-med-2020","paper-keynote-355-lancet-2020","paper-ascent-nejm-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Neoadjuvant TROP2 ADC + pembrolizumab achieves non-inferior pCR and EFS to KEYNOTE-522 with fewer grade 3+ toxicities.","rationale":"ADC payloads are the same chemotherapy class delivered more selectively; ADC-induced immunogenic death complements pembrolizumab.","test":"Randomised phase 3 versus KEYNOTE-522 regimen with pCR then EFS endpoints; TIL-high and HER2-low subgroups pre-specified.","maturity":"early-clinical"},"route":"/ideas/idea-neoadjuvant-adc-io/","neighbours":{"pairing":[{"id":"adc-plus-io","kind":"pairing","name":"ADC + checkpoint inhibitor","route":"/pairings/adc-plus-io/"}],"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/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"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/"}],"trial":[{"id":"keynote-522","kind":"trial","name":"KEYNOTE-522","route":"/trials/keynote-522/"},{"id":"scarlet-s2212","kind":"trial","name":"SCARLET (SWOG S2212)","route":"/trials/scarlet-s2212/"}],"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-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/"}]}}