{"entity":{"id":"patritumab-deruxtecan","kind":"drug","name":"Patritumab deruxtecan","aka":[],"tldr":"A HER3-directed ADC with Enhertu's payload, active in lung and all subtypes of breast cancer, but with a bumpy regulatory road.","summary":"HERTHENA-Lung01 in EGFR-mutant NSCLC after TKI (ORR ~30%) led to a BLA that received a complete response letter in 2024 over manufacturing; HERTHENA-Lung02 phase 3 was positive for PFS but not OS. In breast cancer, HERTHENA-BC dose-expansion data at ESMO Breast 2026 showed activity across HR+/HER2-, HER2+, and TNBC. Daiichi Sankyo and Merck partnership.","status":"phase-3","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov: trials of Patritumab deruxtecan","url":"https://clinicaltrials.gov/search?intr=HER3-DXd"}],"tags":[],"related":[],"cancers":["nsclc","tnbc","breast-hr-positive","egfr-mutant-nsclc"],"sections":[],"technologies":["adc"],"targets":["her3"],"drugs":[],"companies":["daiichi-sankyo","merck"],"institutions":[],"pathways":[],"terms":["ggfg"],"trials":["nct04619004","nct06172478","nct06731907","nct06469944","nct07286149","nct07060807","nct06797635","nct06596694","nct06686394","nct06941272"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"HER3-DXd, U3-1402","modality":"ADC","payload":"DXd","linker":"GGFG cleavable","mechanism":"Anti-HER3 IgG1 with DXd.","approvals":[],"mechanismSteps":["Antibody binds HER3 on the tumour cell surface","Receptor-ADC complex is internalised by endocytosis","Trafficked to the lysosome; linker is cleaved or antibody degraded","DXd is released inside the cell","Topoisomerase-I is trapped on DNA; replication forks collapse into double-strand breaks","Tumour cell dies by apoptosis","Membrane-permeable payload diffuses to kill neighbouring antigen-negative cells (bystander effect)"],"dosing":{"route":"IV infusion","schedule":"5.6 mg/kg every 3 weeks","monitoring":"ILD, blood counts","source":"https://clinicaltrials.gov/study/NCT04619004"},"toxicity":[{"event":"Neutropenia"},{"event":"Thrombocytopenia"},{"event":"Nausea"},{"event":"Fatigue"},{"event":"ILD/pneumonitis"}],"access":[{"country":"US","reimbursement":"Investigational; BLA withdrawn May 2025 after HERTHENA-Lung02 OS result","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2021-12-23","type":"designation","region":"US","note":"Breakthrough Therapy designation, EGFR-mutant NSCLC after TKI and platinum","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2023-12","type":"filing","region":"US","note":"BLA submitted (HERTHENA-Lung01)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2024-06-26","type":"crl","region":"US","note":"Complete response letter citing third-party manufacturing inspection","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2025-05","type":"withdrawal","region":"US","note":"BLA withdrawn after HERTHENA-Lung02 met PFS but not OS","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}]},"route":"/drugs/patritumab-deruxtecan/","neighbours":{"cancer":[{"id":"egfr-mutant-nsclc","kind":"cancer","name":"EGFR-mutated non-small-cell lung cancer","route":"/cancers/egfr-mutant-nsclc/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"tnbc-metastatic","kind":"cancer","name":"Metastatic triple-negative breast cancer","route":"/cancers/tnbc-metastatic/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"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/"}],"target":[{"id":"her3","kind":"target","name":"HER3","route":"/targets/her3/"}],"company":[{"id":"daiichi-sankyo","kind":"company","name":"Daiichi Sankyo","route":"/companies/daiichi-sankyo/"},{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"term":[{"id":"dxd","kind":"term","name":"DXd","route":"/terms/dxd/"},{"id":"ggfg","kind":"term","name":"Tetrapeptide GGFG (maleimide-GGFG-aminomethyl)","route":"/terms/ggfg/"},{"id":"topoisomerase-i-payloads","kind":"term","name":"Topoisomerase-I inhibitor payloads","route":"/terms/topoisomerase-i-payloads/"}],"trial":[{"id":"nct07286149","kind":"trial","name":"A Clinical Study of MK-1084 With Other Treatments for Non-small Cell Lung Cancer (MK-3475-01F)","route":"/trials/nct07286149/"},{"id":"nct07060807","kind":"trial","name":"A Clinical Study of Patritumab Deruxtecan to Treat Breast Cancer (MK-1022-016)","route":"/trials/nct07060807/"},{"id":"nct06172478","kind":"trial","name":"A Study of HER3-DXd in Subjects With Locally Advanced or Metastatic Solid Tumors","route":"/trials/nct06172478/"},{"id":"nct06941272","kind":"trial","name":"A Study of Patritumab Deruxtecan in Pediatric Participants With Relapsed or Refractory Solid Tumors (MK-9999-01C/LIGHTBEAM-U01)","route":"/trials/nct06941272/"},{"id":"nct06731907","kind":"trial","name":"A Study of Pembrolizumab With or Without Chemotherapy in Combination With Additional Treatments for Advanced Non-Small Cell Lung Cancer (NSCLC) (MK-34","route":"/trials/nct06731907/"},{"id":"nct04619004","kind":"trial","name":"HERTHENA-Lung01: Patritumab Deruxtecan in Subjects With Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer","route":"/trials/nct04619004/"},{"id":"herthena-lung02","kind":"trial","name":"HERTHENA-Lung02","route":"/trials/herthena-lung02/"},{"id":"nct06596694","kind":"trial","name":"Study of Patritumab Deruxtecan in Participants With Gastrointestinal Cancers (MK-1022-011) (HERTHENA-PanTumor02)","route":"/trials/nct06596694/"},{"id":"nct06797635","kind":"trial","name":"Study of Patritumab Deruxtecan Plus Pembrolizumab With Other Anticancer Agents in Participants With High-Risk Early-Stage Triple-Negative or Hormone Receptor-Low Positive/HER-2 Negative Breast Cancer (MK-1022-010, HERTHENA-Breast-03)","route":"/trials/nct06797635/"},{"id":"nct06686394","kind":"trial","name":"Study of Patritumab Deruxtecan With Other Anticancer Agents in Participants With HER2 Positive Breast Cancer That Has Spread and Cannot Be Surgically Removed (MK-1022-009)","route":"/trials/nct06686394/"},{"id":"nct06469944","kind":"trial","name":"Substudy 06C: A Study of Investigational Agents With Pembrolizumab (MK-3475) and Chemotherapy in Participants With First-Line Locally Advanced Unresectable/Metastatic Gastroesophageal Adenocarcinoma (MK-3475-06C/KEYMAKER-U06)","route":"/trials/nct06469944/"}],"pairing":[{"id":"tki-then-adc-lung","kind":"pairing","name":"EGFR TKI → ADC on progression","route":"/pairings/tki-then-adc-lung/"}],"person":[{"id":"benjamin-besse","kind":"person","name":"Benjamin Besse","route":"/people/benjamin-besse/"},{"id":"helena-yu","kind":"person","name":"Helena A. Yu","route":"/people/helena-yu/"}],"idea":[{"id":"idea-bio1-stromal-resistance-blockade","kind":"idea","name":"Block the survival signals the tumour's neighbours provide","route":"/ideas/idea-bio1-stromal-resistance-blockade/"}],"pathway":[{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}],"biomarker":[{"id":"her3-expression","kind":"biomarker","name":"HER3 expression","route":"/biomarkers/her3-expression/"}]}}