Enfortumab Vedotin for Bladder Cancer

Recruiting in Palo Alto (17 mi)

+7 other locations

Overseen by Gopakumar Iyer, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing enfortumab vedotin, a drug that targets and kills cancer cells, in patients with upper urinary tract urothelial carcinoma who can't or won't use cisplatin and are planning surgery. Enfortumab vedotin is a new type of drug that targets a specific protein on cancer cells and delivers a substance that kills these cells.

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.

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 a new option for patients with limited treatment choices. ^{1 2 3 4 5}

Is Enfortumab Vedotin safe for humans?

Enfortumab Vedotin, also known as Padcev, has been associated with some serious side effects, including high blood sugar, nerve damage, eye problems, skin reactions, and risks to unborn babies. In studies, 73% of patients experienced severe side effects, and up to 47% had skin reactions. ^{1 2 3 4 6}

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

Enfortumab Vedotin is unique because it is the first drug specifically approved for patients with advanced bladder cancer who have already been treated with PD-1/PD-L1 inhibitors and platinum-based chemotherapy. It works as an antibody-drug conjugate targeting Nectin-4, a protein found on cancer cells, and is administered intravenously. ^{1 2 3 5 6}

Research Team

Gopakumar Iyer, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

Patients who are ineligible for cisplatin based on any of the following criteria: Estimated or calculated creatinine clearance ≥ 30ml/min but < 60 ml/min, Grade 2 or above audiometric hearing loss (per CTCAE v4.0) or declined cisplatin-based neoadjuvant chemotherapy, as documented in medical chart, Availability of tumor specimen block, cell block or 30 unstained slides from diagnosis. Patients with fewer than 30 slides available may be enrolled after discussion with the Principal Investigator. Additional research biopsy is not required, Karnofsky performance status ≥ 70%, Medically appropriate candidate for radical surgery (nephroureterectomy, nephrectomy, or ureterectomy), as per MSK Attending Urologic Oncologist, Age ≥ 18 years.

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.

Trial Timeline

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

Treatment Details

Interventions

• Enfortumab Vedotin (Antibody-drug conjugate)
• Radical surgery (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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Lisa M. DeAngelis

Memorial Sloan Kettering Cancer Center

Chief Medical Officer since 2021

MD from Columbia University

Selwyn M. Vickers

Memorial Sloan Kettering Cancer Center

Chief Executive Officer since 2022

MD from Johns Hopkins University

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

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-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 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-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]

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

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

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

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

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

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

5. 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]

6. Australia pubmed.ncbi.nlm.nih.gov

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