Last updated: August 1, 2026
Padcev (enfortumab vedotin-ejfv, formerly ASG-22ME) is the first-in-class Nectin-4-directed antibody-drug conjugate (ADC), developed by Astellas and Pfizer. It pairs an antibody against Nectin-4 — a protein highly expressed on urothelial (bladder) cancer — with the chemotherapy payload MMAE, delivering that payload directly into the cancer cell. Dosing: intravenous infusion.
Mechanism of action:The antibody binds Nectin-4 on the cancer-cell surface; the ADC is internalized and releases monomethyl auristatin E (MMAE), which disrupts microtubules and triggers cell-cycle arrest and apoptosis. Because Nectin-4 is expressed on nearly all urothelial cancers, enfortumab vedotin is one of the most active single agents in bladder cancer — and Nectin-4 expression in other tumor types is now driving trials beyond the bladder.
Regulatory status:FDA-approved across urothelial cancer: metastatic disease after platinum + immunotherapy (EV-301); first-line locally advanced/metastatic urothelial cancer with pembrolizumab regardless of cisplatin eligibility (Dec 2023, EV-302 / KEYNOTE-A39, overall-survival benefit); and — new on July 10, 2026 — perioperative (neoadjuvant + adjuvant) muscle-invasive bladder cancer with pembrolizumab for all cystectomy candidates (KEYNOTE-B15/EV-304 + KEYNOTE-905/EV-303). The label carries a boxed warning for serious skin reactions (see below).
For decades, bladder cancer was treated with platinum chemotherapy, and options after it failed were limited. Enfortumab vedotin is a different kind of drug: a “guided missile” (antibody-drug conjugate) that homes in on Nectin-4, a marker sitting on the surface of almost all bladder cancers, and delivers a potent chemotherapy payload directly to those cells while largely sparing the rest of the body.
The metastatic story. The biggest shift came in December 2023, when enfortumab vedotin + the immunotherapy pembrolizumab became the first-line standard for advanced/metastatic bladder cancer — the first regimen in decades to beat platinum chemotherapy on overall survival (the EV-302 trial). That combination is now the backbone that most current trials build on.
The 2026 story — moving earlier, toward cure. On July 10, 2026, the FDA extended the same enfortumab vedotin + pembrolizumab regimen into muscle-invasive bladder cancer — earlier-stage disease treated with intent to cure — given before and after surgery to remove the bladder (cystectomy). It's approved now for all patients who are candidates for cystectomy, regardless of whether they can take cisplatin, and is the first platinum-free perioperative regimen in this setting. A major open question the current trials are testing: can patients who respond well keep their bladder altogether?
Enfortumab vedotin's approvals are all in urothelial (bladder) cancer, moving from last-line to first-line to, now, the curative-intent perioperative setting.
1. Perioperative Muscle-Invasive Bladder Cancer, with Pembrolizumab (NEW — July 10, 2026)
2. First-Line Locally Advanced / Metastatic Urothelial Cancer, with Pembrolizumab (EV-302)
3. Metastatic Urothelial Cancer after Platinum + Immunotherapy (EV-301)
★ First-in-Class: A Nectin-4 Guided Missile That Now Reaches Earlier Disease
Enfortumab vedotin is the first and only approved Nectin-4-directed therapy. Nectin-4 is expressed on the large majority of urothelial cancers, which is why the drug is so active in the bladder. What is genuinely new in 2026 is where it is used: the July 10 approval moves the enfortumab vedotin + pembrolizumab regimen out of the metastatic setting and into curative-intent, perioperative treatment of muscle-invasive disease — and does so without platinum chemotherapy, opening the regimen to the many patients who cannot tolerate cisplatin.
The trade-off is a distinctive toxicity profile driven by the ADC payload and Nectin-4 biology: skin reactions (with a boxed warning for severe cases), peripheral neuropathy, high blood sugar, and eye effects — different from the nausea/kidney profile of platinum chemotherapy, and requiring specific monitoring (see below).
Curated set of recruiting interventional enfortumab vedotin / Padcev trials in the ClinTrialFinder corpus as of August 2026 (33 recruiting + 7 not-yet-recruiting), grouped by setting. The registrational KEYNOTE-B15 (NCT04700124) and KEYNOTE-905 trials that supported the July 2026 approval are described above as the approval basis; the trials below are those currently recruiting.
Enfortumab vedotin is built from three parts: a monoclonal antibody that recognizes Nectin-4, a linker, and the cytotoxic payload MMAE (monomethyl auristatin E). Nectin-4 is a cell-adhesion protein expressed at high levels on the surface of nearly all urothelial cancers (and, at varying levels, on some other tumors). When the antibody binds Nectin-4, the whole conjugate is drawn inside the cancer cell, where the linker is cleaved and MMAE is released. MMAE disrupts microtubules — the cell's internal scaffolding needed for division — halting the cell cycle and triggering apoptosis. This “targeted delivery” concentrates a potent chemotherapy inside Nectin-4-positive cells, which is why enfortumab vedotin is one of the most active agents in bladder cancer.
Boxed Warning: Serious Skin Reactions
Enfortumab vedotin carries an FDA boxed warning for serious and sometimes fatal skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Patients are monitored closely for skin changes; treatment is withheld or stopped for severe reactions. Rashes are common and range from mild to life-threatening, so any worsening skin, blistering, or mouth sores must be reported promptly.
Other important effects reflect the drug's mechanism and payload: peripheral neuropathy (numbness/tingling in hands and feet, which can be dose-limiting), hyperglycemia (high blood sugar, which can be severe and includes a risk of diabetic ketoacidosis — blood sugar is monitored, and the drug is used cautiously in diabetes), and ocular disorders (dry eye, corneal changes). Fatigue, hair loss, decreased appetite, and infusion reactions also occur. Enfortumab vedotin is given by intravenous infusion, and management centers on close monitoring of the skin, nerves, blood sugar, and eyes with dose modification as needed.
In advanced/metastatic urothelial cancer, enfortumab vedotin + pembrolizumab is now the first-line standard (EV-302). In muscle-invasive bladder cancer, the July 2026 approval positions enfortumab vedotin + pembrolizumab as perioperative therapy — before and after cystectomy — for cystectomy candidates regardless of cisplatin eligibility. The frontier questions the current trials are testing: whether responders can safely preserve the bladder, how to combine enfortumab vedotin with radiotherapy, what to do after enfortumab vedotin + pembrolizumab (post-EV sequencing), and how far Nectin-4 targeting extends beyond the bladder. For the disease-level view of where enfortumab vedotin sits among all bladder-cancer options, see the bladder cancer trials page.
What is Padcev (enfortumab vedotin) and how does it work?
Padcev (enfortumab vedotin) is the first-in-class Nectin-4-directed antibody-drug conjugate (ADC) from Astellas and Pfizer. Nectin-4 is a protein on the surface of nearly all bladder cancers. The drug is an antibody against Nectin-4 attached to a chemotherapy payload (MMAE); it binds Nectin-4, is taken into the cancer cell, and releases the payload inside to kill it. It is given by IV infusion.
What is Padcev FDA-approved for?
All in bladder (urothelial) cancer: first-line advanced/metastatic disease with pembrolizumab regardless of cisplatin eligibility (Dec 2023, EV-302); metastatic disease after platinum + immunotherapy (EV-301); and, new on July 10, 2026, perioperative (before and after cystectomy) muscle-invasive bladder cancer with pembrolizumab, for all cystectomy candidates.
What changed with the July 2026 approval?
It moved enfortumab vedotin + pembrolizumab into muscle-invasive bladder cancer, given before and after cystectomy, for all patients who are surgery candidates regardless of cisplatin eligibility — the first platinum-free perioperative regimen in this setting. It's based on the KEYNOTE-B15/EV-304 and KEYNOTE-905/EV-303 trials, which showed better event-free and overall survival and much higher pathologic complete-response rates.
What are the main side effects?
The label carries a boxed warning for serious, sometimes fatal skin reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis). Other important effects: peripheral neuropathy (numbness/tingling), high blood sugar (can be severe), and eye problems (dry eye, corneal changes). Close monitoring of skin, nerves, blood sugar, and eyes is standard, with dose changes as needed.
Can Padcev help patients keep their bladder?
That's exactly what several recruiting trials are testing: enfortumab vedotin + pembrolizumab (sometimes with radiotherapy) as a bladder-preserving strategy for muscle-invasive bladder cancer, to avoid removing the bladder in patients who respond well (for example NCT06809140 and NCT07475806). Enfortumab vedotin is also being studied in Nectin-4-expressing cancers beyond the bladder.
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