Enfortumab vedotin
Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) designed to target Nectin-4 (also known as PVRL4), a cell adhesion molecule overexpressed on the surface of various epithelial tumor cells, most notably in urothelial carcinoma and triple-negative breast cancer.
Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) designed to target Nectin-4 (also known as PVRL4), a cell adhesion molecule overexpressed on the surface of various epithelial tumor cells, most notably in urothelial carcinoma and triple-negative breast cancer. The drug consists of a fully human anti-Nectin-4 monoclonal antibody conjugated via a protease-cleavable linker to monomethyl auristatin E (MMAE), a potent microtubule-disrupting cytotoxic agent. Upon binding to Nectin-4 on tumor cell surfaces, the ADC is internalized, the linker is cleaved by lysosomal proteases, and MMAE is released intracellularly to inhibit tubulin polymerization and induce apoptosis.
Enfortumab vedotin received regulatory approval for the treatment of locally advanced or metastatic urothelial carcinoma in patients who have previously received platinum-containing chemotherapy and a programmed death receptor-1 (Programmed cell death 1 (PD-1)) or CD274 molecule inhibitor. Its clinical development has since expanded into earlier lines of therapy, perioperative settings, and combination regimens with checkpoint inhibitors such as pembrolizumab, reflecting the drug's broad potential in Nectin-4-expressing malignancies.
Where the papers sit
14 papers from the last 6 months study enfortumab vedotin directly · updated from PubMed 2 Oct 2026
Study type 2 clinical trials · 9 observational · 1 human data · 1 preclinical · 1 unclassified
Themes 3 themes · 1 new direction
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Real-World Urothelial Care
Real-world care is testing enfortumab vedotin plus pembrolizumab across older and medically diverse patients with advanced or metastatic urothelial carcinoma. Effectiveness and progression-free survival are weighed against toxicity, treatment discontinuation, and structured symptom burden. Eosinophil proportion is being explored as a biomarker for adverse events, while outcomes are compared with avelumab maintenance. The evidence remains observational and heterogeneous, leaving optimal sequencing and management after toxicity unresolved.
7 papers · 50%
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Early-Line Bladder Cancer Therapy
Enfortumab vedotin plus pembrolizumab is moving into earlier-line and perioperative bladder cancer treatment, including cisplatin-ineligible disease. Studies compare it with gemcitabine plus cisplatin and examine cost-effectiveness, pathologic complete response, and survival. Responses are reported in muscle-invasive and upper-tract urothelial cancers, including node-positive disease. The unresolved question is how to select patients and position the regimen against established cisplatin-based therapy.
4 papers · 28.6%
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PD-1 Combination Antitumor Activity
PD-1 blockade is being paired with enfortumab vedotin to increase antitumor activity in recurrent or metastatic cancer. Pembrolizumab combinations are assessed through objective response rate, follow-up, and survival outcomes across head and neck squamous cell carcinoma and urothelial carcinoma. Preclinical work links the combination to enfortumab-induced immunogenic cell death. Whether this benefit translates consistently across tumor types and frontline settings remains open.
3 papers · 21.4%
Enfortumab vedotin is presented as an immune-priming treatment rather than only a cytotoxic ADC
The preclinical urothelial cancer models studied enfortumab vedotin as a Nectin-4-directed ADC and found that its MMAE payload induced immunogenic cell death, increased activated immune cells in the tumor microenvironment, protected mice against tumor rechallenge after vaccination with treated cells, and complemented PD-1 inhibition 42685702Sep. This gives enfortumab vedotin a role outside the set’s usual therapeutic categories of direct tumor-cell killing and clinical combination treatment: it can also function as an inducer of antitumor immunity, providing a mechanistic basis for combining it with immune checkpoint blockade.
Papers
The 14 papers from the last 6 months that study enfortumab vedotin directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
Real-World Urothelial Care (7)
- Structured Symptom Monitoring During Enfortumab Vedotin Plus Pembrolizumab for Advanced or Metastatic Urothelial Carcinoma: Multicenter Retrospective Study. Anticancer research · 1 Oct 2026 PMID 42823162
- Eosinophil Proportion May Serve as a Candidate Biomarker for Adverse Events in Patients With Urothelial Carcinoma Treated With Enfortumab Vedotin. Cancer medicine · 2 Sept 2026 PMID 42681561
- Clinical Outcomes of Metastatic Urothelial Carcinoma Patients Discontinuing Enfortumab Vedotin Due to Toxicity and/or Clinical Response. Clinical genitourinary cancer · 19 Aug 2026 PMID 42618453
- Effectiveness and Safety of Enfortumab Vedotin Plus Pembrolizumab for Patients Aged 80 Years and Older With Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study. Anticancer research · 29 Jul 2026 PMID 42527056
- Real-world safety and effectiveness of enfortumab vedotin plus pembrolizumab in locally advanced or metastatic urothelial carcinoma: A multicenter Japanese cohort study. Urologic oncology · 17 Jul 2026 PMID 42469056
- Effectiveness and safety of enfortumab vedotin and pembrolizumab in a real-world patient population with urothelial carcinoma: results from a multi-institutional cohort (GUARDIANS). Cancer immunology, immunotherapy : CII · 12 Jul 2026 PMID 42437411
- Real-world Comparison of Avelumab Maintenance and Enfortumab Vedotin Plus Pembrolizumab in Metastatic Urothelial Carcinoma. Anticancer research · 29 Jun 2026 PMID 42373274
Early-Line Bladder Cancer Therapy (4)
- Cost-effectiveness of perioperative pembrolizumab plus enfortumab vedotin for cisplatin-ineligible or cisplatin-declining patients with muscle-invasive bladder cancer in the United States. Journal of medical economics · 18 Aug 2026 PMID 42610318
- Enfortumab Vedotin and Pembrolizumab in Cisplatin-Eligible Bladder Cancer. The New England journal of medicine · 22 Jul 2026 PMID 42485627
- First-Line Enfortumab Vedotin Plus Pembrolizumab vs Gemcitabine Plus Cisplatin for Metastatic Urothelial Carcinoma. JAMA network open · 1 Jul 2026 PMID 42384383
- Pathologic Complete Response After Enfortumab Vedotin Plus Pembrolizumab in Node-positive Upper Tract Urothelial Carcinoma. In vivo (Athens, Greece) · 28 Apr 2026 PMID 42049426
PD-1 Combination Antitumor Activity (3)
- Real-world Outcomes of First-line Enfortumab Vedotin Plus Pembrolizumab in Elderly Patients With Advanced Urothelial Carcinoma. Anticancer research · 1 Oct 2026 PMID 42823175
- Enfortumab vedotin induces immunogenic cell death and shows enhanced preclinical antitumor activity when combined with a PD-1 inhibitor. Cell reports. Medicine · 2 Sept 2026 PMID 42685702
- Enfortumab Vedotin plus Pembrolizumab as First-line Treatment in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Results from EV-202 Cohort 9. Clinical cancer research : an official journal of the American Association for Cancer Research · 5 May 2026 PMID 42084607
By study type
Clinical trials (2)
- Enfortumab Vedotin and Pembrolizumab in Cisplatin-Eligible Bladder Cancer. The New England journal of medicine · 22 Jul 2026 PMID 42485627
- Enfortumab Vedotin plus Pembrolizumab as First-line Treatment in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Results from EV-202 Cohort 9. Clinical cancer research : an official journal of the American Association for Cancer Research · 5 May 2026 PMID 42084607
Observational studies and case reports (9)
- Real-world Outcomes of First-line Enfortumab Vedotin Plus Pembrolizumab in Elderly Patients With Advanced Urothelial Carcinoma. Anticancer research · 1 Oct 2026 PMID 42823175
- Structured Symptom Monitoring During Enfortumab Vedotin Plus Pembrolizumab for Advanced or Metastatic Urothelial Carcinoma: Multicenter Retrospective Study. Anticancer research · 1 Oct 2026 PMID 42823162
- Eosinophil Proportion May Serve as a Candidate Biomarker for Adverse Events in Patients With Urothelial Carcinoma Treated With Enfortumab Vedotin. Cancer medicine · 2 Sept 2026 PMID 42681561
- Clinical Outcomes of Metastatic Urothelial Carcinoma Patients Discontinuing Enfortumab Vedotin Due to Toxicity and/or Clinical Response. Clinical genitourinary cancer · 19 Aug 2026 PMID 42618453
- Effectiveness and Safety of Enfortumab Vedotin Plus Pembrolizumab for Patients Aged 80 Years and Older With Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study. Anticancer research · 29 Jul 2026 PMID 42527056
- Real-world safety and effectiveness of enfortumab vedotin plus pembrolizumab in locally advanced or metastatic urothelial carcinoma: A multicenter Japanese cohort study. Urologic oncology · 17 Jul 2026 PMID 42469056
- First-Line Enfortumab Vedotin Plus Pembrolizumab vs Gemcitabine Plus Cisplatin for Metastatic Urothelial Carcinoma. JAMA network open · 1 Jul 2026 PMID 42384383
- Real-world Comparison of Avelumab Maintenance and Enfortumab Vedotin Plus Pembrolizumab in Metastatic Urothelial Carcinoma. Anticancer research · 29 Jun 2026 PMID 42373274
- Pathologic Complete Response After Enfortumab Vedotin Plus Pembrolizumab in Node-positive Upper Tract Urothelial Carcinoma. In vivo (Athens, Greece) · 28 Apr 2026 PMID 42049426
Human data, design not indexed (1)
- Cost-effectiveness of perioperative pembrolizumab plus enfortumab vedotin for cisplatin-ineligible or cisplatin-declining patients with muscle-invasive bladder cancer in the United States. Journal of medical economics · 18 Aug 2026 PMID 42610318
Preclinical: animal, cell and lab studies (1)
- Enfortumab vedotin induces immunogenic cell death and shows enhanced preclinical antitumor activity when combined with a PD-1 inhibitor. Cell reports. Medicine · 2 Sept 2026 PMID 42685702
Unclassified: not yet indexed with MeSH (1)
- Effectiveness and safety of enfortumab vedotin and pembrolizumab in a real-world patient population with urothelial carcinoma: results from a multi-institutional cohort (GUARDIANS). Cancer immunology, immunotherapy : CII · 12 Jul 2026 PMID 42437411
Written from 14 PubMed abstracts, each one listed by PMID above. Published: 2026-07-13. Last written: 2026-09-04 by GPT. Drafted by language models from published abstracts; not medical advice.