{"entity":{"id":"raludotatug-deruxtecan","kind":"drug","name":"Raludotatug deruxtecan","aka":[],"tldr":"Raludotatug deruxtecan is a CDH6 ADC in phase 3 for platinum-resistant ovarian cancer.","summary":"Raludotatug deruxtecan is an anti-CDH6 IgG1 antibody linked through a cleavable GGFG linker to DXd, a topoisomerase I inhibitor that traps the enzyme on DNA and collapses replication forks; the payload crosses membranes, giving a bystander effect. CDH6 is a cadherin overexpressed in ovarian and renal cell carcinoma with little normal-tissue expression. Developed by Daiichi Sankyo with Merck, it produced an objective response rate around 46 percent in phase 1 in heavily pretreated ovarian cancer, and the REJOICE-Ovarian01 phase 2/3 trial is comparing it with chemotherapy in platinum-resistant disease at 5.6 mg/kg every 3 weeks. Nausea, fatigue, neutropenia and anaemia are the main toxicities, with interstitial lung disease monitored as for other DXd conjugates. Whether the response rate holds in a randomised trial is the open question for platinum-resistant ovarian cancer.","status":"phase-3","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov: trials of Raludotatug deruxtecan","url":"https://clinicaltrials.gov/search?intr=R-DXd"}],"tags":[],"related":[],"cancers":["ovarian","rcc"],"sections":[],"technologies":["adc"],"targets":["cdh6"],"drugs":[],"companies":["daiichi-sankyo","merck"],"institutions":[],"pathways":[],"terms":["ggfg"],"trials":["nct06843447","nct06864169","nct06780085","nct06660654"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"R-DXd, DS-6000","modality":"ADC","payload":"DXd","linker":"GGFG cleavable","mechanism":"Anti-CDH6 IgG1 with DXd.","approvals":[],"mechanismSteps":["Antibody binds CDH6 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 (phase 2/3 dose)","monitoring":"ILD, blood counts","source":"https://clinicaltrials.gov/study/NCT06161025"},"toxicity":[{"event":"Nausea"},{"event":"Fatigue"},{"event":"Neutropenia"},{"event":"Anaemia"}],"access":[{"country":"US","reimbursement":"Investigational (REJOICE-Ovarian01)","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2024-10","type":"filing","region":"US","note":"Merck co-development of R-DXd under the Daiichi Sankyo alliance","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"}]},"route":"/drugs/raludotatug-deruxtecan/","neighbours":{"cancer":[{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"platinum-resistant-ovarian-cancer","kind":"cancer","name":"Platinum-resistant ovarian cancer","route":"/cancers/platinum-resistant-ovarian-cancer/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"target":[{"id":"cdh6","kind":"target","name":"CDH6","route":"/targets/cdh6/"}],"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":"nct06843447","kind":"trial","name":"A Clinical Study of Raludotatug Deruxtecan in People With Ovarian Cancer (MK-5909-003)","route":"/trials/nct06843447/"},{"id":"nct06780085","kind":"trial","name":"A Study of Investigational Agents in Participants With Previously Treated Stage IV Nonsquamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01H/KEYMAKER-U01)","route":"/trials/nct06780085/"},{"id":"nct06864169","kind":"trial","name":"A Study of Raludotatug Deruxtecan (R-DXd) in People With Gastrointestinal Cancers (MK-5909-005)","route":"/trials/nct06864169/"},{"id":"nct06660654","kind":"trial","name":"A Study of Raludotatug Deruxtecan in Participants With Advanced/Metastatic Solid Tumors (REJOICE-PanTumor01)","route":"/trials/nct06660654/"},{"id":"rejoice-ovarian01","kind":"trial","name":"REJOICE-Ovarian01","route":"/trials/rejoice-ovarian01/"}]}}