Enfortumab Vedotin + Pembrolizumab for Bladder Cancer

Recruiting at 2 trial locations

Overseen By Ahran Lee

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Matthew Galsky

Must not be taking: Antidepressants, Immunosuppressants, Steroids, others

Disqualifiers: Neuropathy, Diabetes, Autoimmune, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 18

47 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments, enfortumab vedotin and pembrolizumab, for individuals with muscle-invasive bladder cancer. The study aims to determine if this combination can effectively shrink tumors and improve patient outcomes. Participants will initially receive a set of treatments and, if they respond well, will proceed to a maintenance phase. This trial may suit someone with muscle-invasive bladder cancer who has recently undergone surgery to remove bladder tumors. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant findings.

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 certain treatments like systemic steroids or immunosuppressive therapy, you may need to adjust or stop them before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of enfortumab vedotin and pembrolizumab has been tested for safety in patients with muscle-invasive bladder cancer. Results so far indicate that this treatment is generally well-tolerated. One study found no new safety concerns, meaning patients did not experience unexpected side effects beyond what was already known.

It is important to remember that some side effects can still occur, as with any treatment. These might include tiredness, skin rash, or changes in blood test results. However, these are common and usually manageable.

Since this trial is in phase 2, earlier studies demonstrated it was safe enough to test in more patients. This is a positive sign for those considering participation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about enfortumab vedotin combined with pembrolizumab for bladder cancer because this combo targets the disease in a unique way. Enfortumab vedotin is an antibody-drug conjugate that specifically delivers a toxic payload to cancer cells, minimizing damage to healthy cells. Pembrolizumab, an immune checkpoint inhibitor, boosts the body's immune response against cancer cells. Together, they offer a dual approach: directly attacking the cancer and enhancing the immune system's ability to fight it, which could potentially lead to better outcomes compared to traditional treatments like chemotherapy or surgery.

What evidence suggests that enfortumab vedotin plus pembrolizumab could be an effective treatment for bladder cancer?

Research has shown that using enfortumab vedotin with pembrolizumab holds promise for treating muscle-invasive bladder cancer (MIBC). In this trial, participants will receive this combination treatment. Studies have found that this combination can significantly reduce the risk of cancer progression or death. For patients unable to undergo chemotherapy, this treatment has proven especially effective. It is even approved as a first-choice treatment for certain advanced bladder cancers. Overall, enfortumab vedotin and pembrolizumab work together to target and attack cancer cells more effectively than some traditional treatments. ^{2 4 6 7 8}

Who Is on the Research Team?

Matthew Galsky, MD

Principal Investigator

Sponsor-Investigator

Are You a Good Fit for This Trial?

This trial is for adults over 18 with muscle-invasive bladder cancer (MIBC), specifically urothelial cancer, without spread to lymph nodes or distant organs. Participants must have had a complete resection of the bladder tumor and be fit for radical cystectomy. They should also have normal organ function, including specific blood cell counts, and be in good physical condition with an ECOG Performance Status of 0-1.

Inclusion Criteria

I have signed the consent form and agreed to share my health information.

My white blood cell count is within a healthy range.

My hemoglobin level is 9 g/dL or higher.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive 3 cycles of induction enfortumab vedotin plus pembrolizumab

9 weeks

3 visits (in-person)

Restaging

Restaging including MRI of the bladder, urine cytology, and cystoscopy with TURBT of any visible tumor and/or resection site plus random biopsies

1-2 weeks

1 visit (in-person)

Maintenance Treatment

Participants achieving a clinical complete response receive 14 cycles of maintenance treatment with enfortumab vedotin during the first 6 cycles and pembrolizumab for all 14 cycles

42 weeks

14 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Enfortumab Vedotin
• Pembrolizumab

Trial Overview The study tests Enfortumab Vedotin plus Pembrolizumab in MIBC patients. It involves three cycles of these drugs followed by restaging procedures. Those who respond completely continue 'maintenance' treatment for up to 14 cycles; non-responders undergo surgery. The goal is to see if this drug combination can spare some patients from having their bladders removed.

How Is the Trial Designed?

Group I: Enfortumab vedotin plus pembrolizumab Experimental Treatment 2 Interventions

Patients with MIBC will receive 3 cycles (C1-C3) of induction enfortumab vedotin (1.25 mg/kg for a maximum dose of 125 mg) plus pembrolizumab (200 mg) followed by restaging including MRI of the bladder, urine cytology, and cystoscopy with TURBT of any visible tumor and/or resection site plus random biopsies using a recommended template. Patients achieving a stringently defined cCR (defined below) will receive 14 cycles of "maintenance" treatment. Enfortumab vedotin (1.25 mg/kg for a maximum dose of 125 mg) will be administered during the first 6 cycles (C4-C9) of "maintenance" treatment and pembrolizumab (200 mg) will be given all 14 cycles (C4-C14). Patients with any residual disease at clinical restaging (i.e., \>cTa disease) will undergo cystectomy.

Who Is Running the Clinical Trial?

Matthew Galsky

Lead Sponsor

Trials

12

Recruited

470+

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 Inc

Industry Sponsor

Trials

700

Recruited

236,000+

Headquarters

Tokyo, Japan

Top Products

- Xtandi (enzalutamide) for prostate cancer, - Xospata (gilteritinib) for AML, - Padcev (enfortumab vedotin) for bladder cancer, - Prograf (tacrolimus) for organ rejection prevention

Tadaaki Taniguchi

Astellas Pharma Inc

Chief Medical Officer since 2023

MD, PhD

Naoki Okamura

Astellas Pharma Inc

Chief Executive Officer since 2023

University of Tokyo, Faculty of Pharmacy

Icahn School of Medicine at Mount Sinai

Collaborator

Trials

933

Recruited

579,000+

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

Published Research Related to This Trial

Enfortumab vedotin, an antibody drug conjugate for advanced urothelial carcinoma, can cause extravasation leading to serious skin reactions like bullae and cellulitis, as seen in two reported cases.

Both patients successfully managed their cellulitis conservatively and resumed treatment without further complications, suggesting that with proper management, the risks associated with extravasation can be mitigated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug extravasation with Enfortumab vedotin. Grant, CR., de Kouchkovsky, D., Kalebasty, AR., 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, a treatment for advanced bladder cancer, can cause severe skin reactions, with a case report highlighting a patient who developed toxic epidermal necrolysis shortly after starting the drug.

The case emphasizes the need for careful monitoring of skin reactions and suggests that if such reactions occur, treatment may need to be reduced or stopped to prevent serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis after the administration of enfortumab vedotin for urinary bladder urothelial carcinoma. Mimura, Y., Kobayashi, A., Utazu, H., 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) 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 (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]

In a study of 34 patients with metastatic urothelial carcinoma treated with enfortumab vedotin, 56% showed a partial response or stable disease, with a median overall survival of 16 months and progression-free survival of 9 months, indicating its efficacy in a real-world setting.

The treatment was associated with a high incidence of adverse events, with 76% of patients experiencing some level of toxicity, primarily skin-related, but the safety profile was consistent with findings from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab vedotin following platinum-based chemotherapy and immune checkpoint inhibitors for advanced urothelial carcinoma: response, survival and safety analysis from a multicentre real-world Japanese cohort. Miyake, M., Nishimura, N., Oda, Y., 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]

Enfortumab vedotin showed a 44% overall response rate in a phase II trial involving 125 patients with locally advanced or metastatic urothelial carcinoma who had previously undergone platinum-based chemotherapy and PD-1 or PD-L1 checkpoint inhibitor treatment.

While nearly all patients experienced treatment-related adverse events, most of these side effects were mild to moderate, indicating a manageable safety profile for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin Checks Urothelial Cancer. [2020]

Citations

1. urotoday.com urotoday.com/conference-highlights/esmo-2025/esmo-2025-bladder-cancer/164060-esmo-2025-perioperative-enfortumab-vedotin-ev-plus-pembrolizumab-pembro-in-participants-with-muscle-invasive-bladder-cancer-mibc-who-are-cisplatin-ineligible-the-phase-3-keynote-905-study.html

ESMO 2025: Perioperative Enfortumab Vedotin (EV) plus ... Dr. Christof Vulsteke presented the LBA2 - Perioperative (enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder ...

2. ajmc.com ajmc.com/view/enfortumab-vedotin-plus-pembro-cuts-risk-of-disease-progression-death-60-for-patients-with-mibc-who-can-t-have-chemo-with-bladder-removal

Enfortumab Vedotin Plus Pembro Cuts Risk of Disease ... Combination therapy with enfortumab vedotin and pembrolizumab significantly reduces progression and mortality risk of muscle invasive bladder ...

3. annalsofoncology.org annalsofoncology.org/issue/S0923-7534(25)X0011-9?pageStart=61

September 2025 3102P Outcomes with enfortumab vedotin and pembrolizumab in ... Muscle-Invasive Bladder Cancer (MIBC): Updated data and preliminary outcomes for recurrence.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06470282

Enfortumab Vedotin and Pembrolizumab Combined With ... Giving enfortumab vedotin with pembrolizumab and radiation therapy may work better in treating patients with muscle invasive bladder cancer. Detailed ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.745

Clinical efficacy of enfortumab vedotin-pembrolizumab (EV ... The combination of EV-P therapy has recently been approved as first-line (1L) therapy for patients with LA/mUC based on the results of the EV-302 trial.

6. onclive.com onclive.com/view/perioperative-enfortumab-vedotin-plus-pembrolizumab-displays-positive-topline-data-in-muscle-invasive-bladder-cancer

Perioperative Enfortumab Vedotin Plus Pembrolizumab ... Enfortumab vedotin plus pembrolizumab significantly improved survival outcomes in patients with muscle-invasive bladder cancer who were ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.664

EV-302: Updated analysis from the phase 3 global study of ... Results confirm durable EV+P efficacy with no new safety signals, reinforcing EV+P as SOC for the 1L treatment of pts with la/mUC.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06470282?intr=Pembrolizumab%20%2B%20Enfortumab%20Vedotin%20&page=3&rank=23

NCT06470282 | Enfortumab Vedotin and Pembrolizumab ... Giving enfortumab vedotin with pembrolizumab and radiation therapy may work better in treating patients with muscle invasive bladder cancer. Detailed ...