Enfortumab Vedotin + Pembrolizumab vs. Chemotherapy for Bladder Cancer

(EV-302 Trial)

Not currently recruiting at 333 trial locations
SG
SI
Overseen BySeagen Inc. Trial Information Support
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: Astellas Pharma Global Development, Inc.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining two drugs, enfortumab vedotin and pembrolizumab, to treat bladder cancer that has spread beyond the urinary system. It aims to determine if these drugs are more effective than standard chemotherapy treatments. Suitable participants have advanced bladder cancer that cannot be surgically removed and have not received certain prior treatments. As a Phase 3 trial, this study represents the final step before FDA approval, providing patients with access to potentially groundbreaking 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 must not have received certain cancer treatments recently, and you cannot be on systemic antimicrobial treatment for an active infection at the time of randomization.

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

Research shows that using enfortumab vedotin and pembrolizumab together may help treat certain bladder cancers. Studies have found that this combination can lead to better results for patients compared to traditional chemotherapy.

Regarding safety, enfortumab vedotin and pembrolizumab are generally well-tolerated. Clinical studies report common side effects such as tiredness, skin rash, and changes in blood cell counts, while serious side effects occur less frequently. This suggests the combination might be a safe option for many patients.

Both enfortumab vedotin and pembrolizumab have been widely studied in other contexts. The FDA has already approved pembrolizumab for several types of cancer, which enhances understanding of its safety. While every treatment carries risks, current evidence supports the safety of these drugs in the studied groups.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about Enfortumab vedotin combined with pembrolizumab for bladder cancer because it introduces a novel approach to treatment. Unlike traditional chemotherapy, Enfortumab vedotin is an antibody-drug conjugate targeting a protein called Nectin-4, which is prevalent on bladder cancer cells. This targeted delivery allows for more direct cancer cell destruction while potentially sparing healthy cells. Pembrolizumab, on the other hand, is an immunotherapy that helps the immune system recognize and attack cancer cells. Together, these treatments offer a promising alternative to standard chemotherapy regimens like gemcitabine with cisplatin or carboplatin, potentially leading to improved outcomes for patients.

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

Research shows that the combination of enfortumab vedotin and pembrolizumab, which participants in this trial may receive, holds promise for treating advanced bladder cancer. Earlier studies found that this combination reduced the risk of death by 50% and extended patient survival. Tumors shrank or stopped growing in about 67% of patients who received these drugs. Many patients experienced positive outcomes, with some achieving partial or complete recovery. This evidence suggests that this drug combination may effectively manage advanced bladder cancer. Meanwhile, another group in this trial will receive a chemotherapy regimen of gemcitabine with either cisplatin or carboplatin, serving as the active comparator.26789

Who Is on the Research Team?

ZW

Zejing Wang, MD, PhD

Principal Investigator

Seagen Inc.

JL

John Lu, MD

Principal Investigator

Seagen Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced urothelial cancer that has spread, who can handle cisplatin or carboplatin chemo and haven't had certain treatments before. They need to have a performance status score of 0-2, which means they're up and about more than half the day.

Inclusion Criteria

My cancer can be measured and has grown outside the area treated with radiation or after it.
I haven't had systemic therapy for advanced bladder cancer, except if it's been over a year since my last treatment.
My blood counts and organ functions are within normal ranges.
See 8 more

Exclusion Criteria

I have an active eye infection or corneal ulcer.
My cancer has spread to my brain.
I have been treated with enfortumab vedotin or similar drugs before.
See 17 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enfortumab vedotin and pembrolizumab or standard chemotherapy

Up to 39.2 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 7.4 years

What Are the Treatments Tested in This Trial?

Interventions

  • Carboplatin
  • Cisplatin
  • Enfortumab vedotin
  • Gemcitabine
  • Pembrolizumab
Trial Overview The study tests enfortumab vedotin plus pembrolizumab against standard chemotherapy alone in treating metastatic bladder cancer. It aims to see if the combination works better for patients whose disease has spread beyond their urinary system.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm AExperimental Treatment2 Interventions
Group II: Arm BActive Control3 Interventions

Carboplatin is already approved in United States, European Union, Canada for the following indications:

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Approved in United States as Paraplatin for:
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Approved in European Union as Carboplatin for:
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Approved in Canada as Carboplatin for:

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

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

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

Published Research Related to This Trial

Enfortumab vedotin, an antibody-drug conjugate targeting the Nectin-4 antigen on urothelial carcinoma cells, has shown promising results in clinical trials, leading to its accelerated approval by the FDA for patients with advanced bladder cancer who have already received prior treatments.
The combination of enfortumab vedotin with the checkpoint inhibitor pembrolizumab has received breakthrough therapy designation from the FDA, indicating its potential as a first-line treatment for patients unable to receive cisplatin, highlighting its efficacy in improving treatment options for bladder cancer.
The biology and rationale of targeting nectin-4 in urothelial carcinoma.Heath, EI., Rosenberg, JE.[2023]
In a study of 6007 urothelial cancer patients, those who received enfortumab vedotin after pembrolizumab had significantly longer overall survival compared to those treated with paclitaxel or docetaxel, indicating its effectiveness as a life-prolonging therapy.
Enfortumab vedotin was identified as an independent risk factor for improved overall survival, suggesting it may be a valuable treatment option for Japanese patients with advanced urothelial carcinoma following prior therapies.
Administration of Enfortumab Vedotin after Immune-Checkpoint Inhibitor and the Prognosis in Japanese Metastatic Urothelial Carcinoma: A Large Database Study on Enfortumab Vedotin in Metastatic Urothelial Carcinoma.Kawahara, T., Hasizume, A., Uemura, K., 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.
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]

Citations

PADCEV™ Plus KEYTRUDA™, Given Before and After ...Results from the key secondary endpoint of OS showed a 50% reduction in the risk of death for neoadjuvant and adjuvant PADCEV plus KEYTRUDA as ...
KEYTRUDA® (pembrolizumab) plus Padcev® (enfortumab ...KEYTRUDA® (pembrolizumab) plus Padcev® (enfortumab vedotin-ejfv) Significantly Improved Event-Free and Overall Survival and Pathologic Complete ...
Enfortumab Vedotin With or Without Pembrolizumab in ...The findings suggest that enfortumab vedotin, especially combined with pembrolizumab, offers promising beneficial outcomes in metastatic urothelial carcinoma ...
Clinical efficacy of enfortumab vedotin-pembrolizumab (EV ...The median follow-up time was 7.1 months (IQR: 4.93-9.26). In terms of BOR, 56 patients (46.6%) experienced PR, 34 (28.3%) CR, 12 (10%) PD, 7 ( ...
Padcev and Keytruda Double Bladder Cancer Survival - NCIOverall, tumors shrank or stopped growing in about 67% of participants treated with enfortumab plus pembrolizumab, compared with 44% of those ...
KEYTRUDA® (pembrolizumab) Plus Padcev ... - Merck.comKEYTRUDA® (pembrolizumab) Plus Padcev® (enfortumab vedotin-ejfv) Reduced Risk of Event-Free Survival Events by 60% and Risk of Death by 50% for Certain Patients ...
Perioperative Enfortumab Vedotin Plus Pembrolizumab ...Enfortumab vedotin plus pembrolizumab significantly improved survival outcomes in patients with muscle-invasive bladder cancer who were ...
8.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/38446675/
Enfortumab Vedotin and Pembrolizumab in Untreated ...Conclusions: Treatment with enfortumab vedotin and pembrolizumab resulted in significantly better outcomes than chemotherapy in patients with ...
Clinical Study Results | PADCEV® (enfortumab vedotin-ejfv)See clinical study data for PADCEV® in adults with advanced bladder cancer or cancers of the urinary tract. See full PI, including Serious Side Effects.
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