Enfortumab Vedotin for Bladder Cancer

(EV-103 Trial)

Not currently recruiting at 110 trial locations

Overseen By Seagen, Inc. Trial Information Support

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Astellas Pharma Global Development, Inc.

Must be taking: Pembrolizumab

Must not be taking: PD-1 inhibitors, CTLA-4 inhibitors

Disqualifiers: CNS metastases, Uncontrolled diabetes, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, enfortumab vedotin, for treating bladder cancer. Researchers aim to evaluate the drug's effectiveness both alone and in combination with other treatments, such as pembrolizumab (an immune therapy) and chemotherapy drugs. The trial focuses on various stages of bladder cancer, including cases where it has spread to other areas or invaded the bladder muscle. It suits individuals with advanced bladder cancer that is either metastatic or muscle-invasive and who have not received certain prior treatments. The study also seeks to identify the side effects of these drug combinations. As a Phase 1, Phase 2 trial, it examines how the treatment works in people and measures its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study showed that enfortumab vedotin, an experimental drug for bladder cancer, demonstrated promising safety results and helped patients live longer compared to standard chemotherapy. Real-world evidence from Europe also supports its use alone for advanced urothelial cancer, indicating it is generally well-tolerated.

When combined with pembrolizumab, an immune therapy, enfortumab vedotin has received approval for treating advanced urinary system cancers. This combination improved survival rates and was deemed safe enough for FDA approval. However, some patients experienced side effects such as skin reactions and diarrhea, which are common with both drugs.

The combination of enfortumab vedotin with other chemotherapy drugs like cisplatin, carboplatin, and gemcitabine has also undergone testing. These studies provide early insights into safety, but the full safety profile is still under evaluation. Enfortumab vedotin is already approved for other cancer treatments, suggesting a certain level of established safety. However, as with any drug, side effects can occur, and patient reactions may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Enfortumab Vedotin for bladder cancer because it offers a unique mechanism of action compared to traditional treatments like chemotherapy. Unlike standard chemotherapy, which indiscriminately targets rapidly dividing cells, Enfortumab Vedotin is an antibody-drug conjugate that specifically targets Nectin-4, a protein highly expressed in bladder cancer cells. This targeted approach allows for more precise attack on cancer cells while potentially reducing harm to normal cells. Additionally, when combined with Pembrolizumab, an immunotherapy drug, it can enhance the body's own immune response to fight cancer, potentially offering improved outcomes for patients who might not benefit from standard chemotherapy alone.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that enfortumab vedotin, one of the treatments in this trial, holds promise for advanced bladder cancer. Studies have found it can extend patients' lives compared to standard chemotherapy. In this trial, some participants will receive enfortumab vedotin combined with pembrolizumab, which has demonstrated a high success rate, with 68% of patients responding well. This combination also extends survival, particularly for those unable to undergo certain types of chemotherapy. Other participants will receive enfortumab vedotin with platinum-based drugs like cisplatin or carboplatin, which also provide strong survival benefits. Overall, these treatments offer hope for people battling bladder cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Changting Meng, MD

Principal Investigator

Seagen Inc.

Jason Lukas, MD, PhD

Principal Investigator

Seagen Inc.

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Enfortumab Vedotin
• Gemcitabine
• Pembrolizumab

Trial Overview The 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.

How Is the Trial Designed?

Group I: Randomized Cohort K: Enfortumab Vedotin Monotherapy Experimental Treatment 1 Intervention

Enfortumab vedotin on days 1 and 8 every 21 days

Group II: Randomized Cohort K: Enfortumab Vedotin + Pembrolizumab Experimental Treatment 2 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 setting Experimental Treatment 2 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 2L Experimental Treatment 2 Interventions

Enfortumab vedotin and gemcitabine on days 1 and 8 every 21 days

Group V: Optional Cohort B: Enfortumab Vedotin + Pembrolizumab in 2L Experimental Treatment 2 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 2L Experimental Treatment 2 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 setting Experimental Treatment 1 Intervention

Enfortumab vedotin on days 1 and 8 and every 21 days

Group VIII: Cohort H: Enfortumab vedotin in MIBC neoadjuvant setting Experimental Treatment 1 Intervention

Enfortumab vedotin on days 1 and 8 every 21 days

Group IX: Cohort G: Enfortumab Vedotin + Platinum + Pembrolizumab in 1L Experimental Treatment 4 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 1L Experimental Treatment 2 Interventions

Enfortumab vedotin on days 1 and 8 plus carboplatin on day 1 every 21 days

Group XI: Cohort D: Enfortumab Vedotin + Cisplatin in 1L Experimental Treatment 2 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 1L Experimental Treatment 2 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

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

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

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

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

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

Published Research Related to This Trial

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 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]

In the EV-201 trial involving 125 patients with advanced urothelial carcinoma, enfortumab vedotin (EV) demonstrated a stable health-related quality of life (HRQoL) throughout treatment, with no worsening of global health status or physical functioning.

Patients who responded to EV therapy reported lower pain and fatigue levels, particularly those with bone metastases, suggesting potential improvements in symptoms alongside the treatment's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. McGregor, B., O'Donnell, PH., Balar, A., et al.[2023]

The combination of enfortumab vedotin (EV) and pembrolizumab (Pembro) demonstrated a high confirmed objective response rate (cORR) of 64.5% in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer, indicating its efficacy as a first-line treatment option.

Patients receiving the combination therapy also experienced durable responses, with 65.4% maintaining their response at 12 months, while the safety profile showed manageable adverse events, with no new safety signals identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. O'Donnell, PH., Milowsky, MI., Petrylak, DP., et al.[2023]

Enfortumab vedotin (EV) and platinum rechallenge both demonstrated comparable oncological outcomes in patients with advanced urothelial carcinoma after prior treatments, with progression-free survival (PFS) and overall survival (OS) rates being similar between the two groups.

In a study of 64 patients, both treatments showed effective results, suggesting that EV can be a viable alternative to platinum rechallenge for patients who have already undergone platinum-based chemotherapy and pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab vedotin versus platinum rechallenge in post-platinum, post-pembrolizumab advanced urothelial carcinoma: A multicenter propensity score-matched study. Taguchi, S., Kawai, T., Ambe, Y., 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]

In a study of 45 patients with locally advanced or metastatic urothelial cancer, the combination of enfortumab vedotin and pembrolizumab resulted in tumor shrinkage in 73% of patients within 2 months, with effects lasting over 2 years.

While 16% of patients experienced serious side effects, most were manageable, although 24% had to stop treatment due to these side effects, indicating a need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A plain language summary exploring a new treatment combination for untreated locally advanced or metastatic urothelial cancer: enfortumab vedotin plus pembrolizumab. Hoimes, CJ., Flaig, TW., Milowsky, MI., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11842279/

Real‐Life Impact of Enfortumab Vedotin or Chemotherapy in ... EV has been demonstrated to be more efficacious than chemotherapy in terms of overall survival (OS), progression‐free survival (PFS) and overall ...

2. urotoday.com urotoday.com/conference-highlights/asco-2025/asco-2025-bladder-cancer/161056-asco-2025-treatment-patterns-and-clinical-outcomes-with-platinum-based-chemotherapy-after-enfortumab-vedotin-and-pembrolizumab-in-patients-with-metastatic-urothelial-carcinoma.html

ASCO 2025: Treatment Patterns and Clinical Outcomes ... Among the 46 patients who received platinum-based chemotherapy following progression on EV+P, the overall response rate (ORR) was 49%. Response ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4573

Treatment patterns and clinical outcomes with platinum- ... 16 patients had disease response to EV/P (observed response rate [ORR] 42%, 95% CI 27%, 59%). 36 patients (95%) received doublet therapy with ...

4. onclive.com onclive.com/view/enhanced-bladder-cancer-outcomes-stem-from-individualized-first-line-regimens

Enhanced Bladder Cancer Outcomes Stem From ... When patients [in that trial were] treated [with this regimen, the overall response rate (ORR) was] 67.7% [95% CI, 63.1%-72.1%]. 2 That's an ...

5. oncologynewscentral.com oncologynewscentral.com/bladder-cancer/questions-about-enfortumab-vedotin-for-bladder-cancer-answered-by-real-world-data-expert-says

Questions About Enfortumab Vedotin for Bladder Cancer ... Enfortumab vedotin has shown consistent efficacy in advanced urothelial carcinoma across treatment lines, including in patients previously ...

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. 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.

8. 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).

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

Clinical Review - Enfortumab Vedotin (Padcev) - NCBI - NIH The National Cancer Data Base report on bladder carcinoma. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer.

10. 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 ...