Enfortumab Vedotin + Pembrolizumab vs. Chemotherapy for Bladder Cancer

(EV-302 Trial)

Recruiting at 266 trial locations

Overseen By Seagen Inc. Trial Information Support

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Astellas Pharma Global Development, Inc.

Must not be taking: MMAE-based ADCs, PD-(L)-1 inhibitors

Disqualifiers: Uncontrolled diabetes, CNS metastases, others

No Placebo Group All 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 Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 39.2 months

886 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is being done to see how well two drugs (enfortumab vedotin and pembrolizumab) work together to treat patients with urothelial cancer. The study will compare these drugs to other drugs that are usually used to treat this cancer (standard of care). The patients in this study will have cancer that has spread from their urinary system to other parts of their body.

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.

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

Research shows that both Enfortumab Vedotin and Pembrolizumab have individually improved survival in urothelial cancer, and their combination is being studied as a first-line treatment for patients who cannot use cisplatin. Enfortumab Vedotin has shown response rates of 40% to 52% in patients with advanced urothelial cancer, including those with poor prognosis. ^{1 2 3 4 5}

Is the combination of Enfortumab Vedotin and Pembrolizumab safe for humans?

The combination of Enfortumab Vedotin and Pembrolizumab has been studied in patients with advanced urothelial cancer and is generally well tolerated. Common side effects include skin issues, fatigue, and high blood sugar, which are usually manageable with care and dose adjustments. However, peripheral neuropathy (nerve damage) can be a limiting factor, and rare serious skin reactions have been reported. ^{1 3 4 6 7}

What makes the drug combination of Enfortumab Vedotin and Pembrolizumab unique for bladder cancer?

This drug combination is unique because it offers a first-line treatment option for patients with advanced bladder cancer who cannot use the standard cisplatin-based chemotherapy, and it targets a specific protein (nectin-4) on cancer cells, potentially improving survival outcomes. ^{1 2 3 7 8}

Research Team

Zejing Wang, MD, PhD

Principal Investigator

Seagen Inc.

John Lu, MD

Principal Investigator

Seagen Inc.

Eligibility Criteria

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.

I had chemotherapy after bladder surgery and my cancer returned more than a year later.

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.

Timeline

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

Treatment Details

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.

Participant Groups

Group I: Arm A Experimental Treatment 2 Interventions

Enfortumab vedotin + pembrolizumab

Group II: Arm B Active Control 3 Interventions

Gemcitabine + cisplatin or carboplatin

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular 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

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

Findings from Research

In a study of 45 cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer, the combination of enfortumab vedotin and pembrolizumab resulted in a high confirmed objective response rate of 73.3%, indicating significant tumor shrinkage.

The treatment demonstrated a manageable safety profile, with most adverse events being manageable, and showed promising median durations of response and overall survival of 25.6 months and 26.1 months, respectively, suggesting its potential as an effective first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer. Hoimes, CJ., Flaig, TW., Milowsky, MI., 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]

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]

Enfortumab vedotin (EV) is an FDA-approved treatment for patients with treatment-refractory urothelial cancer, showing overall response rates of 40% to 52%, even in patients with poor prognosis due to visceral metastasis.

EV is generally well tolerated, especially in patients who cannot receive cisplatin, though it can cause manageable side effects like skin toxicity and peripheral neuropathy, which may limit dosage in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Treatment of Locally Advanced and Metastatic Urothelial Cancer: Enfortumab Vedotin in Context. Hoffman-Censits, J., Maldonado, L.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

In a study of 140 patients with non-metastatic muscle-invasive bladder cancer, both gemcitabine plus cisplatin (Gem/Cis) and gemcitabine plus carboplatin (Gem/Carbo) regimens showed similar rates of complete clinical response (cCR) before surgery, indicating that both treatments are effective in this context.

However, patients receiving Gem/Cis had significantly better overall survival (OS) compared to those on Gem/Carbo, with median OS of 41 months versus 26 months, suggesting that while both regimens are effective, Gem/Cis may offer a survival advantage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncological Outcomes of Neoadjuvant Gemcitabine plus Carboplatin versus Gemcitabine plus Cisplatin in Locally Advanced Bladder Cancer: A Retrospective Analysis. Mofid, B., Razzaghdoust, A., Ghajari, M., et al.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The biology and rationale of targeting nectin-4 in urothelial carcinoma. Heath, EI., Rosenberg, JE.[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]

References

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

Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer. [2023]

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

Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. [2023]

3. England 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. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Targeted Treatment of Locally Advanced and Metastatic Urothelial Cancer: Enfortumab Vedotin in Context. [2022]

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

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. [2023]

6. Iran pubmed.ncbi.nlm.nih.gov

Oncological Outcomes of Neoadjuvant Gemcitabine plus Carboplatin versus Gemcitabine plus Cisplatin in Locally Advanced Bladder Cancer: A Retrospective Analysis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

The biology and rationale of targeting nectin-4 in urothelial carcinoma. [2023]

8. Australia pubmed.ncbi.nlm.nih.gov

Enfortumab vedotin versus platinum rechallenge in post-platinum, post-pembrolizumab advanced urothelial carcinoma: A multicenter propensity score-matched study. [2023]