Intravesical Enfortumab Vedotin for Bladder Cancer

Recruiting at 29 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

58 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for bladder cancer by delivering the drug directly into the bladder through a thin tube. The study will determine the best dose and evaluate its effectiveness and side effects.

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.

What data supports the effectiveness of the drug Enfortumab Vedotin for bladder cancer?

Enfortumab Vedotin has been shown to be effective in treating advanced bladder cancer, with a study reporting a 44% response rate in patients who had previously received other treatments. This drug works by targeting a protein on cancer cells and delivering a toxin to kill them, offering improved survival for patients with limited options. ^{1 2 3 4 5}

Is enfortumab vedotin safe for humans?

Enfortumab vedotin has been associated with several side effects, including high blood sugar, nerve damage, eye problems, skin reactions, and risks to unborn babies. Serious skin reactions occurred in up to 47% of patients, and severe side effects were seen in 73% of patients in one study. ^{1 2 3 6 7}

What makes the drug Enfortumab Vedotin unique for bladder cancer treatment?

Enfortumab Vedotin is unique because it is an antibody-drug conjugate that targets Nectin-4, a protein found on cancer cells, and is specifically approved for patients with advanced bladder cancer who have already been treated with other therapies like PD-1/PD-L1 inhibitors and platinum-based chemotherapy. It is administered intravenously and has shown a significant response rate in patients who have limited treatment options. ^{1 2 3 7 8}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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 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]

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, 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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin-ejfv: A First-in-Class Anti-Nectin-4 Antibody-Drug Conjugate for the Management of Urothelial Carcinoma. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Enfortumab vedotin-ejfv for the treatment of advanced urothelial carcinoma. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Somatic alterations of TP53 and MDM2 associated with response to enfortumab vedotin in patients with advanced urothelial cancer. [2023]

6. United States 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. [2022]

7. Australia pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis after the administration of enfortumab vedotin for urinary bladder urothelial carcinoma. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin: Nursing Perspectives on the Management of Adverse Events in Patients With Locally Advanced or Metastatic Urothelial Carcinoma. [2021]