Enfortumab Vedotin for Bladder Cancer

Recruiting at 8 trial locations

Overseen By Scot Niglio, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: HAART therapy

Must not be taking: MMAE-based ADCs

Disqualifiers: Metastatic disease, Uncontrolled diabetes, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 9 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if enfortumab vedotin (also known as Padcev) is a safe and effective treatment for people with urothelial carcinoma, a type of bladder cancer affecting the upper urinary tract, who cannot or choose not to receive the chemotherapy drug cisplatin. Participants will receive enfortumab vedotin before undergoing standard surgery to remove their tumor. Ideal candidates are those diagnosed with this specific cancer type, planning for surgery, and unable to use cisplatin.

As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on therapeutic anticoagulation (blood thinners), you must be on a stable dose. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that enfortumab vedotin is likely to be safe for humans?

Research has shown that enfortumab vedotin has been tested in people with advanced bladder cancer and other urinary tract cancers. These studies indicate that the treatment is generally well-tolerated. Although some patients experienced side effects, the treatment proved more effective than traditional chemotherapy. Reports highlight that enfortumab vedotin can help delay cancer progression.

In earlier research, enfortumab vedotin, used alone or with another drug called pembrolizumab, reduced the risk of death by nearly half compared to chemotherapy. While side effects like tiredness or skin reactions can occur, these studies suggest that enfortumab vedotin is a promising treatment option for people with advanced bladder cancer who cannot receive standard chemotherapy. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

Unlike the standard treatments for bladder cancer, which often include chemotherapy or immunotherapy, Enfortumab Vedotin is unique because it specifically targets a protein called Nectin-4, which is commonly found on bladder cancer cells. This targeted approach allows the drug to deliver its cancer-killing payload directly to the tumor cells, potentially reducing harm to healthy cells and leading to fewer side effects. Researchers are excited because Enfortumab Vedotin’s targeted mechanism could offer a more effective and potentially less toxic option for patients, potentially improving outcomes for those who do not respond well to existing therapies.

What evidence suggests that enfortumab vedotin might be an effective treatment for bladder cancer?

Research has shown that enfortumab vedotin, which participants in this trial will receive, works effectively against advanced bladder cancer. Studies have found that it extends patients' lives more than standard chemotherapy. One study demonstrated that combining enfortumab vedotin with another cancer drug, pembrolizumab, reduced the risk of death by 49%. For patients with metastatic cancer, it shrank the cancer in over half of the cases, achieving a 52% overall response rate. These findings suggest that enfortumab vedotin could be a promising treatment for urothelial carcinoma in the upper urinary tract. ^{1 2 3 5 6}

Who Is on the Research Team?

Scot Niglio, MD, MS

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with high-grade urothelial carcinoma of the upper urinary tract who can't or choose not to take cisplatin and are planning on having surgery. They should have adequate kidney function, hearing loss no worse than Grade 2, a good performance status, stable blood counts and liver enzymes, and not be pregnant or breastfeeding. People with uncontrolled diabetes, recent major surgery, active heart disease or infections like tuberculosis or hepatitis B/C cannot join.

Inclusion Criteria

My blood counts and liver function tests are within the required ranges, and if I have HIV, it's under control.

I have a specific type of bladder cancer that has not spread beyond my pelvis.

Exclusion Criteria

My cancer has spread to other parts of my body.

I've had chemo or radiation for bladder cancer in the last 2 years.

I had a heart attack in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enfortumab vedotin at 1.25 g/kg on days 1 and 8 of a 21-day cycle, for a total of three cycles

9 weeks

6 visits (in-person)

Surgery

Participants undergo radical nephroureterectomy, ureterectomy, or nephrectomy, depending on the site of the tumor

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Enfortumab Vedotin
• Radical surgery

Trial Overview The study is testing Enfortumab Vedotin's effectiveness and safety in treating cancer before patients undergo standard radical surgery to remove their tumors. It targets those who aren't eligible for cisplatin chemotherapy.

How Is the Trial Designed?

Group I: Enfortumab Vedotin Experimental Treatment 2 Interventions

All patients will receive enfortumab vedotin at 1.25 g/kg on days 1 and 8 of 21 days cycle, for a total of three cycles, followed by radical nephroureterectomy, ureterectomy, or nephrectomy, depending on the site of the tumor and per the clinical decision of the treating urologist.

Enfortumab Vedotin is already approved in United States, European Union for the following indications:

Approved in United States as Padcev for:

• Locally advanced or metastatic urothelial cancer

Approved in European Union as Padcev for:

• Locally advanced or metastatic urothelial cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Astellas Pharma US, Inc.

Industry Sponsor

Trials

90

Recruited

12,900+

Naoki Okamura

Astellas Pharma US, Inc.

Chief Executive Officer since 2023

Not available

Tadaaki Taniguchi

Astellas Pharma US, Inc.

Chief Medical Officer since 2023

MD, PhD

Published Research Related to This Trial

Enfortumab vedotin-ejfv (EV) is an effective treatment for locally advanced or metastatic urothelial carcinoma (UC), showing a 44% overall response rate and a median overall survival of 11.7 months in heavily pretreated patients.

While EV demonstrates significant antitumor activity, it also presents unique toxicity concerns that require careful monitoring, highlighting the need for further studies to optimize its use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin-ejfv: A First-in-Class Anti-Nectin-4 Antibody-Drug Conjugate for the Management of Urothelial Carcinoma. Halford, Z., Anderson, MK., Clark, MD.[2021]

Enfortumab vedotin (PADCEV) received accelerated FDA approval for treating locally advanced or metastatic urothelial cancer in patients who have already undergone specific prior therapies, based on substantial evidence from a study involving 125 patients.

The treatment showed a confirmed objective response rate of 44%, with a median response duration of 7.6 months, although 73% of patients experienced grade 3-4 adverse reactions, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma. Chang, E., Weinstock, C., Zhang, L., et al.[2022]

Enfortumab vedotin-ejfv (EV) is an effective treatment option for adults with locally advanced or metastatic urothelial carcinoma who have already received PD-1/PD-L1 inhibitors and platinum-based chemotherapy, as it targets the Nectin-4 protein.

To maximize the benefits of EV therapy, it is crucial to educate patients and caregivers, monitor for adverse events, and intervene promptly to manage any side effects that may arise during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin: Nursing Perspectives on the Management of Adverse Events in Patients With Locally Advanced or Metastatic Urothelial Carcinoma. Pace, A., Brower, B., Conway, D., et al.[2021]

Enfortumab vedotin, a treatment for advanced bladder cancer, can cause severe skin reactions, with a case report highlighting a patient who developed toxic epidermal necrolysis shortly after starting the drug.

The case emphasizes the need for careful monitoring of skin reactions and suggests that if such reactions occur, treatment may need to be reduced or stopped to prevent serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis after the administration of enfortumab vedotin for urinary bladder urothelial carcinoma. Mimura, Y., Kobayashi, A., Utazu, H., et al.[2023]

Enfortumab vedotin-ejfv is a first-in-class monoclonal antibody drug conjugate that effectively targets Nectin-4 on bladder cancer cells, delivering a toxin that induces cell death, leading to improved overall survival in patients with metastatic urothelial carcinoma who have limited treatment options.

The drug has demonstrated a high response and disease-control rate with an acceptable toxicity profile, making it a significant advancement in the standard of care for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab vedotin-ejfv for the treatment of advanced urothelial carcinoma. Mantia, CM., Sonpavde, G.[2022]

Enfortumab vedotin (Padcev) is the first FDA-approved treatment specifically for adults with locally advanced or metastatic urothelial cancer who have already undergone treatment with PD-1/PD-L1 inhibitors and platinum-based chemotherapy.

This approval marks a significant advancement in cancer therapy, providing a new option for patients who have limited treatment choices after previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves First Agent to Treat Locally Advanced, Metastatic Urothelial Cancer. Kahl, KL.[2023]

Citations

1. padcev.com padcev.com/trial-results

Clinical Study Results | PADCEV® (enfortumab vedotin-ejfv) See clinical study data for PADCEV® in adults with advanced bladder cancer or cancers of the urinary tract. See full PI, including Serious Side Effects.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2035807

Enfortumab Vedotin in Previously Treated Advanced ... Enfortumab vedotin significantly prolonged survival as compared with standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma.

3. urotoday.com urotoday.com/conference-highlights/esmo-2025/esmo-2025-bladder-cancer/164052-esmo-2025-ev-103-cohort-k-efficacy-and-safety-of-enfortumab-vedotin-with-or-without-pembrolizumab-in-cisplatin-ineligible-patients-with-previously-untreated-locally-advanced-or-metastatic-urothelial-cancer-with-a-median-follow-up-of-3-5-years.html

ESMO 2025: EV-103 Cohort K: Efficacy and Safety ... After 5 years of follow-up in the Dose Escalation/Cohort A, EV+P continued to show durable responses and a meaningful survival, with a median OS ...

4. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizer-and-astellas-padcevr-enfortumab-vedotin-ejfv-plus-0

Pfizer and Astellas' PADCEV® (enfortumab vedotin-ejfv) ... Results showed enfortumab vedotin plus pembrolizumab reduced the risk of death by 49% versus chemotherapy (hazard ratio [HR] = 0.51, 95% ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10535083/

Enfortumab vedotin in metastatic urothelial carcinoma After a median follow-up of 13.4 months, ORR (the primary endpoint) was 52%, with a CR rate of 20%. The efficacy was confirmed in all subgroups.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38446675/

Enfortumab Vedotin and Pembrolizumab in Untreated ... Conclusions: Treatment with enfortumab vedotin and pembrolizumab resulted in significantly better outcomes than chemotherapy in patients with ...