Pembrolizumab + Enfortumab Vedotin + Surgery for Bladder Cancer

Not currently recruiting at 327 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Nonurothelial malignancy, Metastatic disease, 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: 18

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment options for individuals with muscle-invasive bladder cancer who cannot or choose not to take cisplatin, a common chemotherapy drug. The study tests the effectiveness of two drugs, pembrolizumab (an immunotherapy drug) and enfortumab vedotin (an antibody-drug conjugate), in combination with surgery, compared to surgery alone. Participants may qualify if they have confirmed bladder cancer that hasn't spread and are unable or unwilling to use cisplatin. The goal is to determine if these drug combinations can help patients live longer without cancer recurrence. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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, if you are on chronic systemic steroid therapy or any other form of immunosuppressive therapy, you may need to stop these at least 7 days before starting the study drug.

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

Research has shown that pembrolizumab is generally well-tolerated by patients with bladder cancer. In one study, 11% of patients stopped treatment due to side effects, such as lung and colon inflammation. However, these side effects were usually managed effectively.

Similarly, studies indicate that enfortumab vedotin, especially when combined with pembrolizumab, is also considered safe. It is approved for certain types of bladder cancer, but like all treatments, it can cause side effects, such as tiredness and skin rash. Overall, both treatments have demonstrated a good balance of effectiveness and safety for bladder cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for bladder cancer because they combine existing therapies in a novel way that could enhance effectiveness. Unlike traditional treatments, which typically involve surgery alone or with chemotherapy, Pembrolizumab and Enfortumab Vedotin work by harnessing the immune system. Pembrolizumab is an immunotherapy that blocks a protein called PD-1, helping the immune system attack cancer cells. Enfortumab Vedotin is an antibody-drug conjugate that targets and delivers a potent chemotherapy directly to the cancer cells. By combining these treatments with surgery, there is potential for a more comprehensive attack on the cancer, which could lead to better outcomes for patients.

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

In this trial, participants will join different treatment arms to evaluate the effectiveness of various therapies for bladder cancer. Research has shown that pembrolizumab, which participants in Arm A and Arm C may receive, helps patients with high-risk bladder cancer live longer. Specifically, after three years, about 61% of patients who received pembrolizumab were still alive, compared to fewer patients who did not receive it. Pembrolizumab also extends the time patients live without any signs of cancer after surgery.

Participants in Arm C will receive a combination of enfortumab vedotin and pembrolizumab. Previous studies have shown promising results for this combination, reducing the risk of death by 49% in patients with advanced bladder cancer compared to standard chemotherapy. Additionally, this combination achieved a 60% complete response, meaning no signs of cancer were found in tissue samples after treatment, highlighting its potential effectiveness in treating bladder cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with muscle-invasive bladder cancer who can't take cisplatin or choose not to. They must be able to undergo surgery, have good organ function, and an ECOG status of 0-2. Women must use effective contraception or abstain from sex if they're of childbearing potential; men also have similar requirements if receiving enfortumab vedotin.

Inclusion Criteria

A WOCBP must have a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention

My bladder cancer has not spread, as confirmed by scans.

My organs are working well.

Exclusion Criteria

My diabetes is not under control.

I have had radiation therapy to my bladder before.

I have received a transplant from another person.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Treatment

Participants receive 3 preoperative cycles of pembrolizumab or enfortumab vedotin + pembrolizumab

9 weeks

3 visits (in-person)

Surgery

Participants undergo radical cystectomy (RC) and pelvic lymph node dissection (PLND)

1 week

1 visit (in-person)

Postoperative Treatment

Participants receive 14 cycles of postoperative pembrolizumab or 6 cycles of enfortumab vedotin + pembrolizumab followed by 8 cycles of pembrolizumab alone

42 weeks

14 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 7.6 years

What Are the Treatments Tested in This Trial?

Interventions

• Enfortumab Vedotin
• Pembrolizumab
• Radical Cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND]

Trial Overview

The study tests perioperative pembrolizumab (a drug) alone or combined with enfortumab vedotin (another drug), plus bladder removal surgery against surgery alone. The goal is to see which approach leads to better survival without the disease progressing.

How Is the Trial Designed?

Group I: Arm C: Enfortumab Vedotin + Pembrolizumab + Surgery Experimental Treatment 1 Intervention

Participants receive 3 preoperative cycles of enfortumab vedotin + pembrolizumab, followed by standard of care surgery, followed by 6 cycles of postoperative enfortumab vedotin + pembrolizumab, followed by 8 cycles of pembrolizumab alone. Each cycle is 21 days.

Group II: Arm A: Pembrolizumab + Surgery Experimental Treatment 2 Interventions

Participants receive 3 preoperative cycles of pembrolizumab, followed by standard of care surgery, followed by 14 cycles of postoperative pembrolizumab. Each cycle is 21 days.

Group III: Arm B: Surgery alone Active Control 1 Intervention

Participants receive standard of care surgery alone.

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?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

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

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

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

Merck Sharp & Dohme LLC

Lead 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

Astellas Pharma Global Development, Inc.

Industry 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

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 (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]

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]

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]

Citations

1.

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.

2.

ncbi.nlm.nih.gov

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

Clinical Review - Enfortumab Vedotin (Padcev) - NCBI - NIH

Totals of 4.9% and 35.8% of patients achieved a confirmed complete response (CR) and partial response (PR), respectively, in the enfortumab vedotin arm compared ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S155876732400257X

Real-world Effectiveness of Single-Agent Enfortumab ...

EV demonstrates efficacy in patients with mUC regardless of prior receipt of platinum-based chemotherapy and PD-1/L1 inhibitors or treatment line.

4.

urotoday.com

urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-press-releases/158093-pfizer-and-astellas-padcev-enfortumab-vedotin-ejfv-plus-keytruda-pembrolizumab-shows-long-term-efficacy-in-first-line-treatment-of-locally-advanced-or-metastatic-urothelial-cancer-la-muc.html

Pfizer and Astellas' PADCEV® (enfortumab vedotin-ejfv) ...

Results showed enfortumab vedotin plus pembrolizumab reduced the risk of death by 49% versus chemotherapy (hazard ratio [HR] = 0.51, 95% ...

5.

onclive.com

onclive.com/view/consolidative-surgery-following-enfortumab-vedotin-plus-pembrolizumab-displays-efficacy-in-advanced-urothelial-carcinoma

Consolidative Surgery Following Enfortumab Vedotin Plus ...

Enfortumab vedotin-ejfv and pembrolizumab, followed by surgery, achieved a 60% complete pathologic response in advanced urothelial carcinoma ...

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.

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).

8.

pfizer.com

pfizer.com/news/press-release/press-release-detail/pfizer-and-astellas-padcevr-enfortumab-vedotin-ejfv-plus-0

Pfizer and Astellas' PADCEV® (enfortumab vedotin-ejfv) ...

The combination of enfortumab vedotin and pembrolizumab was the first approval to offer an alternative to platinum-containing chemotherapy.

9.

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 ...