348 Participants Needed

Enfortumab Vedotin for Bladder Cancer

(EV-103 Trial)

Recruiting at 105 trial locations
SI
Overseen BySeagen, Inc. Trial Information Support
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Astellas Pharma Global Development, Inc.
Must be taking: Pembrolizumab
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called enfortumab vedotin alone and with other treatments in patients with advanced or muscle-invasive bladder cancer. The goal is to see how well these treatments work and what side effects they might have. Enfortumab vedotin targets and kills cancer cells, while pembrolizumab helps the immune system fight the cancer.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on high doses of steroids or other immunosuppressive medications, you may not be eligible to participate.

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

Enfortumab Vedotin has been approved by the FDA for treating advanced bladder cancer after other treatments have been tried, based on a study showing a 44% response rate in patients, with some experiencing complete tumor disappearance. The drug is used when previous treatments, including certain immunotherapies and chemotherapy, have not been successful.12345

Is Enfortumab Vedotin safe for humans?

Enfortumab Vedotin has been shown to have a tolerable safety profile in patients with advanced bladder cancer, but it can cause serious side effects like high blood sugar, nerve damage, eye problems, skin reactions, and risks to unborn babies. In a study, 73% of patients experienced severe side effects.12346

How is the drug Enfortumab Vedotin unique for treating bladder cancer?

Enfortumab Vedotin is unique because it is the first drug approved to treat advanced bladder cancer in patients who have already received other treatments like 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 given through an IV on a specific schedule.12378

Research Team

CM

Changting Meng, MD

Principal Investigator

Seagen Inc.

JL

Jason Lukas, MD, PhD

Principal Investigator

Seagen Inc.

Eligibility Criteria

This trial is for adults with advanced or muscle-invasive urothelial cancer, including bladder and other urinary cancers. Participants should be eligible for certain chemotherapy drugs like cisplatin or carboplatin, and some may also qualify for pembrolizumab treatment. They must not have received specific prior treatments, have a good performance status (able to carry out daily activities), and an expected lifespan of at least 3 months.

Inclusion Criteria

If you are in Cohort J, H, or L, you have not received certain types of treatments for MIBC, but may have had specific bladder treatments in the past. If you are in Cohort J, you may be eligible for pembrolizumab.
I am eligible for pembrolizumab treatment.
You are expected to live for at least 3 more months.
See 17 more

Exclusion Criteria

I have received PD-1, PD-L1, or PD-L2 inhibitors, except if I'm in Cohort F.
I have not taken drugs like CD137 agonists, OX-40 agonists, or CTLA-4 inhibitors for my cancer, except if I'm in Cohort F.
I have had prior treatment with a checkpoint inhibitor.
See 14 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive enfortumab vedotin alone or in combination with pembrolizumab to determine the safety and tolerability

21 days
Visits on days 1 and 8 every 21 days

Expansion

Participants are treated in various cohorts to evaluate the efficacy of enfortumab vedotin in combination with other therapies

Up to 3 years
Visits on days 1 and 8 every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

  • Carboplatin
  • Cisplatin
  • Enfortumab Vedotin
  • Gemcitabine
  • Pembrolizumab
Trial OverviewThe study tests enfortumab vedotin alone or combined with anticancer therapies such as pembrolizumab, cisplatin, carboplatin, and gemcitabine. It aims to see if these treatments can shrink the cancer in patients with locally advanced or metastatic urothelial cancer as well as those with muscle-invasive bladder cancer.
Participant Groups
12Treatment groups
Experimental Treatment
Group I: Randomized Cohort K: Enfortumab Vedotin MonotherapyExperimental Treatment1 Intervention
Enfortumab vedotin on days 1 and 8 every 21 days
Group II: Randomized Cohort K: Enfortumab Vedotin + PembrolizumabExperimental Treatment2 Interventions
Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
Group III: Optional Cohort J:EV+Pembrolizumab in MIBC neoadjuvant settingExperimental Treatment2 Interventions
Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
Group IV: Optional Cohort F: Enfortumab Vedotin+Gemcitabine in 1L and 2LExperimental Treatment2 Interventions
Enfortumab vedotin and gemcitabine on days 1 and 8 every 21 days
Group V: Optional Cohort B: Enfortumab Vedotin + Pembrolizumab in 2LExperimental Treatment2 Interventions
Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
Group VI: EV + Pembrolizumab in cisplatin-ineligible 1L and in 2LExperimental Treatment2 Interventions
Dose Escalation: Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days
Group VII: Cohort L: Enfortumab vedotin in MIBC in perioperative settingExperimental Treatment1 Intervention
Enfortumab vedotin on days 1 and 8 and every 21 days
Group VIII: Cohort H: Enfortumab vedotin in MIBC neoadjuvant settingExperimental Treatment1 Intervention
Enfortumab vedotin on days 1 and 8 every 21 days
Group IX: Cohort G: Enfortumab Vedotin + Platinum + Pembrolizumab in 1LExperimental Treatment4 Interventions
Enfortumab vedotin on days 1 and 8 plus cisplatin or carboplatin on day 1 plus pembrolizumab on day 1 every 21 days
Group X: Cohort E: Enfortumab Vedotin + Carboplatin in 1LExperimental Treatment2 Interventions
Enfortumab vedotin on days 1 and 8 plus carboplatin on day 1 every 21 days
Group XI: Cohort D: Enfortumab Vedotin + Cisplatin in 1LExperimental Treatment2 Interventions
Enfortumab vedotin on days 1 and 8 plus cisplatin on day 1 every 21 days
Group XII: Cohort A: EV + Pembrolizumab in cisplatin-ineligible 1LExperimental Treatment2 Interventions
Enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 every 21 days

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

Find a Clinic Near You

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 profile image

Naoki Okamura

Astellas Pharma Global Development, Inc.

Chief Executive Officer

Not available

Merck Sharp & Dohme LLC

Industry Sponsor

Trials
4,096
Recruited
5,232,000+
Chirfi Guindo profile image

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis profile image

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

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 profile image

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein profile image

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

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.
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.
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.
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]

References

FDA Approves First Agent to Treat Locally Advanced, Metastatic Urothelial Cancer. [2023]
FDA Approval Summary: Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma. [2022]
Enfortumab Vedotin-ejfv: A First-in-Class Anti-Nectin-4 Antibody-Drug Conjugate for the Management of Urothelial Carcinoma. [2021]
A plain language summary exploring a new treatment combination for untreated locally advanced or metastatic urothelial cancer: enfortumab vedotin plus pembrolizumab. [2023]
Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. [2023]
Health-related Quality of Life of Patients with Locally Advanced or Metastatic Urothelial Cancer Treated with Enfortumab Vedotin after Platinum and PD-1/PD-L1 Inhibitor Therapy: Results from Cohort 1 of the Phase 2 EV-201 Clinical Trial. [2023]
Enfortumab vedotin versus platinum rechallenge in post-platinum, post-pembrolizumab advanced urothelial carcinoma: A multicenter propensity score-matched study. [2023]
Enfortumab Vedotin: Nursing Perspectives on the Management of Adverse Events in Patients With Locally Advanced or Metastatic Urothelial Carcinoma. [2021]