Intravesical Enfortumab Vedotin for Bladder Cancer

No longer recruiting at 32 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Astellas Pharma Global Development, Inc.

Must not be taking: Chemotherapy, Immunotherapy, others

Disqualifiers: Muscle-invasive cancer, Metastatic disease, others

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

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

Compensation: Varies

Number of Visits: 15

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called enfortumab vedotin (also known as Padcev) for individuals with non-muscle invasive bladder cancer (NMIBC). The study aims to determine how effectively this drug treats NMIBC and to identify any side effects when administered directly into the bladder. This trial may suit those with NMIBC unresponsive to previous BCG therapy and who are unable or unwilling to undergo bladder removal. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received any systemic anticancer therapy within 4 weeks or intravesical therapy within 6 weeks before starting the study treatment.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that enfortumab vedotin is generally well-tolerated by patients with advanced bladder cancer. Earlier studies found that this drug significantly extended survival compared to standard chemotherapy, suggesting reasonable safety. Its approval for certain advanced bladder cancer cases further supports its safety profile.

However, every drug can have side effects. Enfortumab vedotin commonly causes tiredness, skin rash, and changes in blood cell counts. Serious side effects are less common but can occur. This study aims to assess its safety when used directly in the bladder for the specific type of bladder cancer under investigation.

Participants should weigh the potential benefits and side effects when considering joining the trial. It is crucial to discuss thoroughly with healthcare professionals to make an informed decision. ^{1 2 3 4 5}

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

Enfortumab vedotin is unique because it targets bladder cancer cells using a novel mechanism. Unlike traditional treatments such as chemotherapy or immunotherapy, enfortumab vedotin is an antibody-drug conjugate that specifically delivers a powerful chemotherapy agent directly to the cancer cells. This targeted approach aims to minimize damage to healthy cells, potentially reducing side effects. Researchers are excited about this treatment because it could offer a more effective and tolerable option for patients with bladder cancer.

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

Research has shown that enfortumab vedotin holds promise for treating advanced bladder cancer. In earlier studies, it extended patients' lives compared to standard chemotherapy. Many patients experienced tumor shrinkage, with 4.9% having no detectable cancer and 35.8% showing some tumor reduction. These results suggest that enfortumab vedotin can effectively target cancer cells. In this trial, participants will receive enfortumab vedotin in either a dose escalation or dose expansion cohort. Although the current study focuses on a different type of bladder cancer, these findings offer hope for its effectiveness in non-muscle invasive bladder cancer (NMIBC) as well. ^{2 6 7 8 9}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for people with a type of bladder cancer called NMIBC who have had all visible tumors removed recently, can't or won't get their bladder taken out (radical cystectomy), and whose cancer isn't responding to BCG treatment. They should be able to perform daily activities with little help (ECOG score 0-2). People can't join if they've had radiation for bladder cancer, kidney issues due to the tumor, other recent cancer treatments, muscle-invasive or spread-out urothelial carcinoma.

Inclusion Criteria

More than half of my cancer is urothelial carcinoma.

I cannot or do not want to undergo major bladder surgery.

I can take care of myself and perform daily activities.

Exclusion Criteria

I have upper tract urothelial cancer, confirmed by a recent scan.

My cancer has caused swelling in my kidney due to urine blockage.

I have or had advanced bladder cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive enfortumab vedotin once a week for 6 weeks

6 weeks

6 visits (in-person)

Maintenance

Participants receive enfortumab vedotin once a month for 9 doses

9 months

9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Enfortumab Vedotin

Trial Overview The study tests enfortumab vedotin delivered directly into the bladder through a catheter in patients with NMIBC. It aims to find out how well this drug works and what side effects it may cause when used as a local treatment for this specific type of bladder cancer.

How Is the Trial Designed?

Group I: Enfortumab vedotin: Dose expansion cohort Experimental Treatment 1 Intervention

During the induction phase, participants will receive enfortumab vedotin once a week for 6 weeks. During the maintenance phase, participants will receive enfortumab vedotin once a month for 9 doses.

Group II: Enfortumab vedotin: Dose escalation cohort Experimental Treatment 1 Intervention

During the induction phase, participants will receive enfortumab vedotin once a week for 6 weeks. During the maintenance phase, participants will receive enfortumab vedotin once a month for 9 doses.

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?

Astellas Pharma Global Development, Inc.

Lead Sponsor

Trials

204

Recruited

123,000+

Tadaaki Taniguchi

Astellas Pharma Global Development, Inc.

Chief Medical Officer

M.D., Ph.D.

Naoki Okamura

Astellas Pharma Global Development, Inc.

Chief Executive Officer

Not available

Seagen Inc.

Industry Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Seagen, a wholly owned subsidiary of Pfizer

Industry Sponsor

Trials

20

Recruited

4,900+

Published Research Related to This Trial

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]

In a retrospective study of 304 patients with advanced urothelial cancer, enfortumab vedotin (EV) demonstrated a 52% overall response rate (ORR) in patients treated with EV monotherapy, consistent with previous clinical trial data.

EV was effective across various patient subsets, including those with comorbidities like renal impairment and diabetes, as well as patients with FGFR3 alterations, indicating its potential for broader use in populations often excluded from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of enfortumab vedotin in advanced urothelial cancer: Analysis from the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) study. Koshkin, VS., Henderson, N., James, M., et al.[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]

In a study of 29 patients with advanced urothelial carcinoma treated with enfortumab vedotin, the overall response rate was 41%, with median progression-free survival (PFS) of 5.1 months and overall survival (OS) of 10.2 months, indicating the treatment's efficacy in this difficult-to-treat population.

Patients with specific genetic alterations, particularly in TP53 and MDM2, showed improved response rates and survival outcomes, suggesting these alterations could serve as important biomarkers for predicting treatment efficacy with enfortumab vedotin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Somatic alterations of TP53 and MDM2 associated with response to enfortumab vedotin in patients with advanced urothelial cancer. Jindal, T., Zhu, X., Bose, R., et al.[2023]

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, 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 (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-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]

Citations

1. 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.

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK605113/

Clinical Review - Enfortumab Vedotin (Padcev) - NCBI - NIH Totals of 4.9% and 35.8% of patients achieved a confirmed complete response (CR) and partial response (PR), respectively, in the enfortumab vedotin arm compared ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S155876732400257X

Real-world Effectiveness of Single-Agent Enfortumab ... EV demonstrates efficacy in patients with mUC regardless of prior receipt of platinum-based chemotherapy and PD-1/L1 inhibitors or treatment line.

4. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-press-releases/158093-pfizer-and-astellas-padcev-enfortumab-vedotin-ejfv-plus-keytruda-pembrolizumab-shows-long-term-efficacy-in-first-line-treatment-of-locally-advanced-or-metastatic-urothelial-cancer-la-muc.html

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/PMC11416998/

Cost-effectiveness of first-line enfortumab vedotin in addition ... The combination therapy also reduced the risk of progression or death by 55% and nearly doubled median PFS, with an HR of 0.45 (median PFS: 12.5 ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/761137s018.pdf

Padcev - accessdata.fda.gov Nonclinical data suggest that the anticancer activity of enfortumab vedotin-ejfv is due to the binding of the ADC to Nectin-4-expressing cells, followed by ...

7. aetna.com aetna.com/cpb/medical/data/900_999/0967.html

Enfortumab Vedotin-ejfv (Padcev) - Medical Clinical Policy ... Padcev, in combination with pembrolizumab, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC).

8. 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) ... Nonclinical data suggest the anticancer activity of enfortumab vedotin is due to its binding to Nectin-4-expressing cells, followed by the ...

9. urotoday.com urotoday.com/conference-highlights/asco-gu-2024/asco-gu-2024-bladder-cancer/149388-asco-gu-2024-safety-and-efficacy-of-enfortumab-vedotin-in-patients-with-metastatic-locally-advanced-urothelial-cancer-real-world-evidence-from-a-european-database.html

ASCO GU 2024: Safety and Efficacy of Enfortumab Vedotin ... EV is approved as a single agent treatment option for metastatic urothelial carcinoma patients with disease progression following platinum-based chemotherapy ...