{"entity":{"id":"enfortumab-vedotin","kind":"drug","name":"Enfortumab vedotin","aka":[],"tldr":"Enfortumab vedotin is an ADC against Nectin-4 that, combined with pembrolizumab, nearly doubled survival in advanced bladder cancer.","summary":"EV-302 (2023): enfortumab vedotin plus pembrolizumab versus platinum chemotherapy in first-line advanced urothelial cancer, OS 31.5 vs 16.1 months (HR 0.47). Now the global standard. Being tested in muscle-invasive bladder cancer (EV-303/304, positive in 2025). Rash, neuropathy, and hyperglycaemia are class effects.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Enfortumab_vedotin","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Enfortumab%20vedotin"}],"tags":[],"related":[],"cancers":["urothelial","muscle-invasive-bladder-cancer"],"sections":[],"technologies":["adc"],"targets":["nectin4"],"drugs":[],"companies":["astellas","pfizer"],"institutions":[],"pathways":[],"terms":["mc-vc-pabc"],"trials":["ev-302","nct06483334","nct07815665","nct07720284","nct07475806","nct06305767","nct07421700","nct07566156","nct04225117","nct04960709","nct07287995","nct06493552"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Padcev","modality":"ADC","payload":"MMAE (tubulin inhibitor), DAR ~3.8","linker":"mc-vc-PABC, protease-cleavable","mechanism":"Fully human anti-Nectin-4 IgG1; MMAE released by cathepsin B; bystander killing.","approvals":[{"region":"US","year":2019,"indication":"Advanced urothelial cancer after platinum and PD-1/PD-L1 (accelerated)"},{"region":"US","year":2023,"indication":"First-line advanced urothelial cancer with pembrolizumab"},{"region":"EU","year":2022,"indication":"mUC after platinum + PD-1; 1L with pembrolizumab 2024"}],"mechanismSteps":["Antibody binds Nectin-4 on the tumour cell surface","Receptor-ADC complex is internalised by endocytosis","Trafficked to the lysosome; linker is cleaved or antibody degraded","MMAE is released inside the cell","Microtubule assembly is blocked; mitosis arrests","Tumour cell dies by apoptosis","Membrane-permeable payload diffuses to kill neighbouring antigen-negative cells (bystander effect)"],"dosing":{"route":"IV infusion over 30 min","schedule":"1.25 mg/kg (max 125 mg) days 1, 8, 15 of 28-day cycle (monotherapy) or days 1 and 8 of 21-day cycle with pembrolizumab","modifications":"Hold for grade 3 rash or hyperglycaemia; discontinue for SJS/TEN or grade ≥3 neuropathy","monitoring":"Skin, glucose (HbA1c/BMI risk), neuropathy, eyes","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b5631d3e-4604-4363-8f20-11dfc5a4a8ed"},"toxicity":[{"event":"Rash","anyGradePct":68,"grade3PlusPct":15,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b5631d3e-4604-4363-8f20-11dfc5a4a8ed","note":"EV-302 with pembrolizumab, n=440"},{"event":"Peripheral neuropathy","anyGradePct":67,"grade3PlusPct":8,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b5631d3e-4604-4363-8f20-11dfc5a4a8ed","note":"EV-302 with pembrolizumab, n=440"},{"event":"Fatigue","anyGradePct":51,"grade3PlusPct":6,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b5631d3e-4604-4363-8f20-11dfc5a4a8ed","note":"EV-302 with pembrolizumab, n=440"},{"event":"Pruritus","anyGradePct":41,"grade3PlusPct":1.1,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b5631d3e-4604-4363-8f20-11dfc5a4a8ed","note":"EV-302 with pembrolizumab, n=440"},{"event":"Diarrhoea","anyGradePct":38,"grade3PlusPct":4.5,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b5631d3e-4604-4363-8f20-11dfc5a4a8ed","note":"EV-302 with pembrolizumab, n=440"},{"event":"Alopecia","anyGradePct":35,"grade3PlusPct":0.5,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b5631d3e-4604-4363-8f20-11dfc5a4a8ed","note":"EV-302 with pembrolizumab, n=440"},{"event":"Decreased appetite","anyGradePct":33,"grade3PlusPct":1.8,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b5631d3e-4604-4363-8f20-11dfc5a4a8ed","note":"EV-302 with pembrolizumab, n=440"},{"event":"Weight decrease","anyGradePct":33,"grade3PlusPct":3.6,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b5631d3e-4604-4363-8f20-11dfc5a4a8ed","note":"EV-302 with pembrolizumab, n=440"},{"event":"Dry eye","anyGradePct":24,"grade3PlusPct":0,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b5631d3e-4604-4363-8f20-11dfc5a4a8ed","note":"EV-302 with pembrolizumab, n=440"},{"event":"Hyperglycaemia (grade 3-4 glucose elevation)","grade3PlusPct":14,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b5631d3e-4604-4363-8f20-11dfc5a4a8ed","note":"EV-302 with pembrolizumab, n=440"}],"access":[{"country":"US","reimbursement":"Medicare Part B (physician-administered); commercial plans per formulary","assistance":"https://www.padcev.com/support","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"},{"country":"UK","reimbursement":"NICE: recommended with pembrolizumab for untreated advanced urothelial cancer (2024)","source":"https://www.nice.org.uk/guidance/published?ngt=Technology%20appraisal%20guidance","asOf":"2026-09-06"},{"country":"EU","reimbursement":"EMA approved 2022 (monotherapy), 2024 (with pembrolizumab)","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2018-03","type":"designation","region":"US","note":"Breakthrough Therapy designation","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2019-12-18","type":"accelerated-approval","region":"US","note":"Accelerated approval, advanced urothelial cancer after platinum and PD-1/PD-L1 (EV-201)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications","indication":"Adults with locally advanced or metastatic urothelial cancer who received a PD-1 or PD-L1 inhibitor and a platinum-containing chemotherapy in the neoadjuvant, locally advanced, or metastatic setting"},{"date":"2021-07-09","type":"conversion","region":"US","note":"Full approval and cisplatin-ineligible expansion (EV-301)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications","indication":"Adults with locally advanced or metastatic urothelial cancer who received a PD-1 or PD-L1 inhibitor and a platinum-containing chemotherapy in the neoadjuvant, locally advanced, or metastatic setting"},{"date":"2023-04-03","type":"accelerated-approval","region":"US","note":"Accelerated approval with pembrolizumab, cisplatin-ineligible first line","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications","indication":"In combination with pembrolizumab for the treatment of adult patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-containing chemotherapy"},{"date":"2023-12-15","type":"conversion","region":"US","note":"Full approval with pembrolizumab, all first-line advanced urothelial cancer (EV-302)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications","indication":"In combination with pembrolizumab for the treatment of adult patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-containing chemotherapy"},{"date":"2025-Q4","type":"filing","region":"US","note":"Muscle-invasive bladder cancer (EV-303/304) submissions following positive results","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2026-07-10","type":"approval","region":"US","note":"Muscle-invasive bladder cancer with pembrolizumab, with or without berahyaluronidase alfa","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-or-pembrolizumab-and-berahyaluronidase-alfa-pmph-each-enfortumab-vedotin"}]},"route":"/drugs/enfortumab-vedotin/","neighbours":{"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"muscle-invasive-bladder-cancer","kind":"cancer","name":"Muscle-invasive and advanced bladder cancer","route":"/cancers/muscle-invasive-bladder-cancer/"},{"id":"urethral","kind":"cancer","name":"Urethral cancer","route":"/cancers/urethral/"},{"id":"urethral-urothelial-carcinoma","kind":"cancer","name":"Urothelial carcinoma of the urethra","route":"/cancers/urethral-urothelial-carcinoma/"}],"technology":[{"id":"adc-payload-neutralizer","kind":"technology","name":"ADC payload neutralisers","route":"/technologies/adc-payload-neutralizer/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"adc-supply-chain","kind":"technology","name":"The ADC supply chain (antibody, payload-linker, conjugation, fill)","route":"/technologies/adc-supply-chain/"}],"target":[{"id":"nectin4","kind":"target","name":"Nectin-4","route":"/targets/nectin4/"}],"company":[{"id":"astellas","kind":"company","name":"Astellas","route":"/companies/astellas/"},{"id":"generate-biomedicines","kind":"company","name":"Generate:Biomedicines","route":"/companies/generate-biomedicines/"},{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"term":[{"id":"mc-vc-pabc","kind":"term","name":"mc-Val-Cit-PABC","route":"/terms/mc-vc-pabc/"},{"id":"mmae","kind":"term","name":"MMAE","route":"/terms/mmae/"},{"id":"rash-skin-toxicity","kind":"term","name":"Rash and skin toxicity (acneiform rash, paronychia)","route":"/terms/rash-skin-toxicity/"},{"id":"tubulin-inhibitor-payloads","kind":"term","name":"Tubulin inhibitor payloads","route":"/terms/tubulin-inhibitor-payloads/"}],"trial":[{"id":"nct06305767","kind":"trial","name":"A Clinical Study of Intismeran Autogene (V940) Treatment and Pembrolizumab in People With Bladder Cancer (V940-005/INTerpath-005)","route":"/trials/nct06305767/"},{"id":"nct07287995","kind":"trial","name":"A Study of ASP2998 Given by Itself and Given With Standard Therapies in People With Solid Tumors","route":"/trials/nct07287995/"},{"id":"nct06483334","kind":"trial","name":"A Study of Efficacy and Safety of Sacituzumab Tirumotecan (MK-2870) Plus Enfortumab Vedotin (EV) With and Without Pembrolizumab in Advanced Urothelial Carcinoma (MK-3475-04C/KEYMAKER-U04)","route":"/trials/nct06483334/"},{"id":"nct07815665","kind":"trial","name":"A Study of Ivonescimab in Combination With Enfortumab Vedotin vs Pembrolizumab in Combination With Enfortumab Vedotin in Metastatic Urothelial Carcinoma","route":"/trials/nct07815665/"},{"id":"nct04225117","kind":"trial","name":"A Study to Evaluate Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Malignant Solid Tumors (EV-202)","route":"/trials/nct04225117/"},{"id":"nct07475806","kind":"trial","name":"A Study to Find Out if Enfortumab Vedotin Given With Pembrolizumab Helps People With Muscle-invasive Bladder Cancer Keep Their Bladder","route":"/trials/nct07475806/"},{"id":"nct07720284","kind":"trial","name":"An Open-label Study to Investigate the Efficacy and Safety of Dato-DXd + Rilvegostomig vs SoC in Adult Participants With High-risk MIUC","route":"/trials/nct07720284/"},{"id":"nct07566156","kind":"trial","name":"Enfortumab Vedotin in Combination With Pembrolizumab vs. Concurrent Chemoradiotherapy (cCRT) in People With Muscle Invasive Bladder Cancer (EV-309)","route":"/trials/nct07566156/"},{"id":"ev-302","kind":"trial","name":"EV-302 / KEYNOTE-A39","route":"/trials/ev-302/"},{"id":"ev-303","kind":"trial","name":"EV-303 / KEYNOTE-905","route":"/trials/ev-303/"},{"id":"ev-304","kind":"trial","name":"EV-304 / KEYNOTE-B15","route":"/trials/ev-304/"},{"id":"nct06493552","kind":"trial","name":"Modular Trial of sEphB4-HSA in EphrinB2-High Solid Tumors","route":"/trials/nct06493552/"},{"id":"nct06553885","kind":"trial","name":"Ph II Study of Enfortumab Vedotin in Patients With Advanced or Metastatic CRC or HCC","route":"/trials/nct06553885/"},{"id":"nct07825753","kind":"trial","name":"Protein-Matched ADC or PDC Umbrella Trial in Advanced Pancreatic and Breast Cancer","route":"/trials/nct07825753/"},{"id":"nct07421700","kind":"trial","name":"Symbiotic-GU-06: A Study to Learn About PF-08634404 Alone or In Combination With Enfortumab Vedotin in Urothelial Cancer","route":"/trials/nct07421700/"},{"id":"nct04960709","kind":"trial","name":"Treatment Combination of Durvalumab, Tremelimumab and Enfortumab Vedotin or Durvalumab and Enfortumab Vedotin in Patients With Muscle Invasive Bladder Cancer Ineligible to Cisplatin or Who Refuse Cisplatin","route":"/trials/nct04960709/"}],"pairing":[{"id":"adc-plus-io","kind":"pairing","name":"ADC + checkpoint inhibitor","route":"/pairings/adc-plus-io/"},{"id":"ev-pembro-continuum","kind":"pairing","name":"Enfortumab vedotin + pembrolizumab across the bladder cancer continuum","route":"/pairings/ev-pembro-continuum/"}],"idea":[{"id":"idea-bladder-preservation-mibc","kind":"idea","name":"Bladder preservation for MIBC after perioperative EV + pembrolizumab complete response","route":"/ideas/idea-bladder-preservation-mibc/"},{"id":"idea-reg-hpapi-continuous-flow","kind":"idea","name":"Continuous-flow synthesis of ultra-potent ADC payloads to ease the capacity squeeze","route":"/ideas/idea-reg-hpapi-continuous-flow/"},{"id":"idea-tr1-adc-dose-and-schedule-optimisation","kind":"idea","name":"Dose and schedule optimisation trials specific to antibody-drug conjugates","route":"/ideas/idea-tr1-adc-dose-and-schedule-optimisation/"}],"roadmap":[{"id":"adc-generations","kind":"roadmap","name":"ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs","route":"/roadmaps/adc-generations/"},{"id":"chemotherapy-roadmap","kind":"roadmap","name":"Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs","route":"/roadmaps/chemotherapy-roadmap/"}],"person":[{"id":"lee-jae-lyun","kind":"person","name":"Jae Lyun Lee","route":"/people/lee-jae-lyun/"},{"id":"jonathan-rosenberg","kind":"person","name":"Jonathan E. Rosenberg","route":"/people/jonathan-rosenberg/"},{"id":"shilpa-gupta","kind":"person","name":"Shilpa Gupta","route":"/people/shilpa-gupta/"},{"id":"thomas-powles","kind":"person","name":"Thomas Powles","route":"/people/thomas-powles/"}],"paper":[{"id":"paper-ev-302-nejm-2024","kind":"paper","name":"EV-302: enfortumab vedotin plus pembrolizumab replaces chemotherapy as first treatment for advanced bladder cancer","route":"/key-papers/paper-ev-302-nejm-2024/"}],"pathway":[{"id":"bladder-cancer-signalling","kind":"pathway","name":"Bladder cancer (KEGG map)","route":"/pathways/bladder-cancer-signalling/"},{"id":"drug-efflux-pumps","kind":"pathway","name":"Drug efflux pumps (ABC transporters)","route":"/pathways/drug-efflux-pumps/"},{"id":"mitotic-spindle-checkpoint","kind":"pathway","name":"Mitosis & the spindle assembly checkpoint","route":"/pathways/mitotic-spindle-checkpoint/"}],"biomarker":[{"id":"nectin-4-expression","kind":"biomarker","name":"Nectin-4 expression","route":"/biomarkers/nectin-4-expression/"}]}}