{"entity":{"id":"trastuzumab-emtansine","kind":"drug","name":"Trastuzumab emtansine","aka":[],"tldr":"Trastuzumab emtansine (Kadcyla, T-DM1) was the first ADC for a solid tumour (2013). It is still standard after surgery for HER2+ breast cancer patients whose tumour did not fully respond to pre-surgery treatment.","summary":"Approved 2013 for pretreated HER2+ metastatic breast cancer (EMILIA) and 2019 for residual disease after neoadjuvant therapy (KATHERINE: invasive DFS HR 0.50, with OS benefit). Non-cleavable linker means no bystander effect, which explains its inferiority to T-DXd in DESTINY-Breast03 and its failure in HER2-low disease. Being displaced post-neoadjuvantly by T-DXd (DESTINY-Breast05).","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Trastuzumab_emtansine","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Trastuzumab%20emtansine"}],"tags":[],"related":["her2-ihc-3-plus"],"cancers":["breast-her2-positive","her2-positive-early-breast-cancer"],"sections":[],"technologies":["adc"],"targets":["her2"],"drugs":[],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["smcc"],"trials":["nct06313086","nct06830889","nct06316531","nct05081609","nct06324357","nct04931342","nct04873362","nct00781612","nct06126640"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Kadcyla","code":"T-DM1","modality":"ADC","payload":"DM1 (maytansinoid, tubulin inhibitor), DAR ~3.5","linker":"SMCC, non-cleavable","mechanism":"Trastuzumab with lysine-conjugated DM1; released as Lys-MCC-DM1 after lysosomal degradation, cell-impermeable.","approvals":[{"region":"US","year":2013,"indication":"HER2+ metastatic breast cancer after trastuzumab and taxane"},{"region":"US","year":2019,"indication":"Adjuvant HER2+ breast cancer with residual disease after neoadjuvant therapy"}],"mechanismSteps":["Antibody binds HER2 on the tumour cell surface","Receptor-ADC complex is internalised by endocytosis","Trafficked to the lysosome; linker is cleaved or antibody degraded","DM1 (lysine-MCC-DM1, non-permeable) is released inside the cell","Microtubule assembly is blocked; mitosis arrests","Tumour cell dies by apoptosis"],"dosing":{"route":"IV infusion","schedule":"3.6 mg/kg every 3 weeks; 14 cycles in the adjuvant setting","modifications":"Reduce to 3 then 2.4 mg/kg for thrombocytopenia, hepatotoxicity, neuropathy; discontinue for LVEF <40%","monitoring":"LFTs and platelets before each dose; LVEF every 3 months","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=23f3c1f4-0fc8-4804-a9e3-04cf25dd302e"},"toxicity":[{"event":"Fatigue","anyGradePct":50,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=23f3c1f4-0fc8-4804-a9e3-04cf25dd302e","note":"KATHERINE (adjuvant)"},{"event":"Nausea","anyGradePct":42,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=23f3c1f4-0fc8-4804-a9e3-04cf25dd302e","note":"KATHERINE (adjuvant)"},{"event":"Transaminases increased","anyGradePct":32,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=23f3c1f4-0fc8-4804-a9e3-04cf25dd302e","note":"KATHERINE (adjuvant)"},{"event":"Musculoskeletal pain","anyGradePct":30,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=23f3c1f4-0fc8-4804-a9e3-04cf25dd302e","note":"KATHERINE (adjuvant)"},{"event":"Haemorrhage","anyGradePct":29,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=23f3c1f4-0fc8-4804-a9e3-04cf25dd302e","note":"KATHERINE (adjuvant)"},{"event":"Thrombocytopenia","anyGradePct":29,"grade3PlusPct":6,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=23f3c1f4-0fc8-4804-a9e3-04cf25dd302e","note":"KATHERINE (adjuvant)"},{"event":"Headache","anyGradePct":28,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=23f3c1f4-0fc8-4804-a9e3-04cf25dd302e","note":"KATHERINE (adjuvant)"},{"event":"Peripheral neuropathy","anyGradePct":28,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=23f3c1f4-0fc8-4804-a9e3-04cf25dd302e","note":"KATHERINE (adjuvant)"},{"event":"Left ventricular dysfunction","anyGradePct":3,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=23f3c1f4-0fc8-4804-a9e3-04cf25dd302e","note":"KATHERINE (adjuvant)"}],"access":[{"country":"US","reimbursement":"Medicare Part B (physician-administered); commercial plans per formulary","assistance":"https://www.genentech-access.com","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"},{"country":"UK","reimbursement":"NICE: recommended for residual invasive disease after neoadjuvant therapy (TA632) and HER2+ metastatic disease (TA458)","source":"https://www.nice.org.uk/guidance/published?ngt=Technology%20appraisal%20guidance","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2013-02-22","type":"approval","region":"US","note":"HER2+ metastatic breast cancer after trastuzumab and taxane (EMILIA); first ADC for a solid tumour","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2019-05-03","type":"approval","region":"US","note":"Adjuvant treatment of HER2+ early breast cancer with residual disease (KATHERINE)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2026-Q2","type":"label-change","region":"US","note":"Displaced post-neoadjuvantly by T-DXd approval (DESTINY-Breast05)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}]},"route":"/drugs/trastuzumab-emtansine/","neighbours":{"biomarker":[{"id":"her2-ihc-3-plus","kind":"biomarker","name":"HER2 IHC 3+ (HER2-positive by immunohistochemistry)","route":"/biomarkers/her2-ihc-3-plus/"},{"id":"her2-ish-amplified","kind":"biomarker","name":"HER2 ISH amplified (ERBB2 gene amplification)","route":"/biomarkers/her2-ish-amplified/"}],"cancer":[{"id":"her2-positive-early-breast-cancer","kind":"cancer","name":"Early HER2-positive breast cancer","route":"/cancers/her2-positive-early-breast-cancer/"},{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"her2-positive-breast-brain-metastases","kind":"cancer","name":"HER2-positive breast cancer with brain metastases","route":"/cancers/her2-positive-breast-brain-metastases/"},{"id":"inflammatory-breast-cancer","kind":"cancer","name":"Inflammatory breast cancer","route":"/cancers/inflammatory-breast-cancer/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"company":[{"id":"nsabp-foundation","kind":"company","name":"NSABP Foundation","route":"/companies/nsabp-foundation/"},{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"term":[{"id":"dm1","kind":"term","name":"DM1","route":"/terms/dm1/"},{"id":"smcc","kind":"term","name":"SMCC (thioether, non-cleavable)","route":"/terms/smcc/"},{"id":"tubulin-inhibitor-payloads","kind":"term","name":"Tubulin inhibitor payloads","route":"/terms/tubulin-inhibitor-payloads/"}],"trial":[{"id":"nct06126640","kind":"trial","name":"A Phase III, Active-Controlled Study of SHR-A1811 Versus Trastuzumab Emtansine (T-DM1) in HER2-Positive Primary Breast Cancer Participants With Residual Invasive Disease Following Neoadjuvant Therapy","route":"/trials/nct06126640/"},{"id":"nct00781612","kind":"trial","name":"A Safety Extension Study of Trastuzumab Emtansine in Participants Previously Treated With Trastuzumab Emtansine Alone or in Combination With Other Anti-Cancer Therapy in One of the Parent Studies","route":"/trials/nct00781612/"},{"id":"nct06316531","kind":"trial","name":"A Study Comparing BL-M07D1 With T-DM1 in Patients With Unresectable Locally Advanced or Metastatic HER2-positive Breast Cancer","route":"/trials/nct06316531/"},{"id":"nct04873362","kind":"trial","name":"A Study Evaluating the Efficacy and Safety of Adjuvant Atezolizumab or Placebo and Trastuzumab Emtansine for Participants With HER2-Positive Breast Cancer at High Risk of Recurrence Following Preoperative Therapy","route":"/trials/nct04873362/"},{"id":"nct04931342","kind":"trial","name":"A Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors","route":"/trials/nct04931342/"},{"id":"nct06830889","kind":"trial","name":"A Study of BL-M07D1 Versus T-DM1 in the Adjuvant Treatment of HER2-positive Breast Cancer With Residual Invasive Cancer After Neoadjuvant Therapy","route":"/trials/nct06830889/"},{"id":"nct05081609","kind":"trial","name":"A Study to Investigate Safety and Tolerability of TransCon IL-2 β/γ Alone or in Combination With Pembrolizumab and/or TransCon TLR7/8 Agonist or Other","route":"/trials/nct05081609/"},{"id":"atempt","kind":"trial","name":"ATEMPT","route":"/trials/atempt/"},{"id":"nct06324357","kind":"trial","name":"Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People Wit","route":"/trials/nct06324357/"},{"id":"cupisco","kind":"trial","name":"CUPISCO","route":"/trials/cupisco/"},{"id":"destiny-breast03","kind":"trial","name":"DESTINY-Breast03","route":"/trials/destiny-breast03/"},{"id":"destiny-breast05","kind":"trial","name":"DESTINY-Breast05","route":"/trials/destiny-breast05/"},{"id":"nct06313086","kind":"trial","name":"DP303c Versus Trastuzumab Emtansine in in Patients With HER2-positive Advanced Breast 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Geyer Jr.","route":"/people/charles-geyer/"},{"id":"eleftherios-mamounas","kind":"person","name":"Eleftherios P. Mamounas","route":"/people/eleftherios-mamounas/"},{"id":"gunter-von-minckwitz","kind":"person","name":"Gunter von Minckwitz","route":"/people/gunter-von-minckwitz/"},{"id":"ian-krop","kind":"person","name":"Ian E. Krop","route":"/people/ian-krop/"},{"id":"javier-cortes","kind":"person","name":"Javier Cortés","route":"/people/javier-cortes/"},{"id":"sara-hurvitz","kind":"person","name":"Sara A. Hurvitz","route":"/people/sara-hurvitz/"},{"id":"kim-sung-bae","kind":"person","name":"Sung-Bae Kim","route":"/people/kim-sung-bae/"}],"paper":[{"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-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/"}],"institution":[{"id":"duke-cancer-institute","kind":"institution","name":"Duke Cancer Institute","route":"/institutions/duke-cancer-institute/"}],"pathway":[{"id":"breast-cancer-signalling","kind":"pathway","name":"Breast cancer (KEGG map)","route":"/pathways/breast-cancer-signalling/"},{"id":"mitotic-spindle-checkpoint","kind":"pathway","name":"Mitosis & the spindle assembly checkpoint","route":"/pathways/mitotic-spindle-checkpoint/"}]}}