Enfortumab Vedotin + Pembrolizumab for Bladder Cancer

Overseen By Ryan Romasko, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fox Chase Cancer Center

Must not be taking: Antimicrobials, Antiretrovirals, High-dose steroids

Disqualifiers: CNS metastases, Diabetes, Autoimmune diseases, 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: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with advanced bladder cancer that cannot be surgically removed. The study aims to assess the effectiveness of combining two drugs, enfortumab vedotin (an antibody-drug conjugate) and pembrolizumab (an immunotherapy), in shrinking tumors. Participants will receive these drugs for about 18 weeks. If the cancer responds well, they may continue with one of the drugs as ongoing therapy. This trial seeks participants with advanced bladder cancer who have not previously received chemotherapy for their metastatic condition. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on high-dose steroids or certain treatments for active infections, you may not be eligible. 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?

A previous study tested the safety of combining enfortumab vedotin and pembrolizumab in patients with advanced bladder cancer. This study included 442 patients who received the treatment. Researchers found that most patients tolerated it well, without severe problems. Some patients experienced side effects, but these were usually manageable. The combination treatment helped patients live longer compared to other treatments, indicating its effectiveness and safety. While all treatments can cause side effects, evidence suggests this combination offers a good balance of safety and effectiveness for many patients. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for bladder cancer?

Researchers are excited about Enfortumab Vedotin combined with Pembrolizumab for bladder cancer because it offers a novel approach by targeting specific cancer cells. Enfortumab Vedotin is an antibody-drug conjugate, which means it delivers a powerful chemotherapy agent directly to cancer cells, minimizing damage to healthy cells. This targeted delivery is different from traditional chemotherapies, which can affect both cancerous and normal cells. Additionally, Pembrolizumab is an immune checkpoint inhibitor that helps the body's immune system recognize and attack cancer cells more effectively. Together, these treatments have the potential to enhance effectiveness and reduce side effects compared to standard chemotherapy options.

What evidence suggests that this treatment might be an effective treatment for bladder cancer?

In this trial, participants will receive a combination of enfortumab vedotin and pembrolizumab. Research has shown that this combination can effectively treat metastatic urothelial carcinoma, a type of bladder cancer. Studies found that it can extend patients' lives to an average of 26.7 months, compared to 14.9 months with enfortumab vedotin alone. The treatment also resulted in a 68% rate of tumor shrinkage. In another study, 46.6% of patients experienced partial tumor shrinkage, while 28.3% saw their tumors disappear completely. These findings suggest that this treatment has strong potential to help patients with this cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

Pooja Ghatalia, MD

Principal Investigator

Fox Chase Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with metastatic urothelial carcinoma who haven't been treated before. They'll receive an initial treatment combo followed by maintenance therapy if they respond well. Specific eligibility details are not provided, but typically include factors like age, health status, and cancer stage.

Inclusion Criteria

Ability to understand and willingness to sign a written informed consent and HIPAA consent document.

Normal organ and marrow function as defined: Absolute neutrophil count > 1,000/mm3 unless patient has constitutional neutropenia, Platelets > 100,000/µl, Hemoglobin > 8.0 g/dL, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5 x upper limit of normal (ULN) or <3.5 x ULN if liver metastases, Creatinine Clearance >20 ml/min.

My bladder cancer cannot be removed with surgery and has been confirmed by tests.

Exclusion Criteria

Other underlying medical condition that would impair the ability of the patient to receive or tolerate the planned treatment and follow-up; any known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study.

Pregnant or breastfeeding.

Uncontrolled intercurrent illness including ongoing or active untreated infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would substantially impair the patient's ability to comply with study requirements. Efforts should be made to provide reasonable accommodations before determining exclusion based on social limitations.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive enfortumab vedotin and pembrolizumab for 6 cycles (approximately 18 weeks). Radiographic assessments occur after 3 and 6 cycles.

18 weeks

6 cycles with visits on Days 1 and 8 of each 21-day cycle

Maintenance

Responding patients receive pembrolizumab every 6 weeks or every 3 weeks for up to 2 years. Radiographic assessments occur every 12 weeks.

Up to 2 years

Follow-up

Participants enter Survival Follow-up upon progression or toxicity requiring cessation of therapy. Long-term Follow-up for those who discontinue early.

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Enfortumab Vedotin
• Pembrolizumab

Trial Overview The trial tests a combination of enfortumab vedotin (EV) and pembrolizumab (P) as initial therapy for bladder cancer, followed by maintenance with P alone. It's a Phase II study to see how effective this regimen is in new patients over up to two years.

How Is the Trial Designed?

Group I: Induction EV + Pembrolizumab Followed by Maintenance Pembrolizumab Experimental Treatment 2 Interventions

Participants will receive induction therapy with enfortumab vedotin (EV) plus pembrolizumab (P) for 6 cycles (approximately 18 weeks). EV will be administered at 1.25 mg/kg IV on Days 1 and 8 of each 21-day cycle (starting dose of 1 mg/kg allowed), and pembrolizumab at 200 mg IV on Day 1 of each cycle. Patients achieving complete or partial response will transition to maintenance pembrolizumab at 400 mg IV every 6 weeks or 200 mg IV every 3 weeks for up to 2 years. Dose modifications for EV are permitted per protocol; no dose adjustments for pembrolizumab. Treatment continues until disease progression, unacceptable toxicity, or completion of maintenance therapy.

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Citations

1. clinical-genitourinary-cancer.com clinical-genitourinary-cancer.com/article/S1558-7673(25)00153-3/fulltext

Real-World Outcomes of Enfortumab Vedotin and ... Most patients were male (71.0%) and white (90.7%). The median progression-free survival was 12.9 months (95% CI, 9.5–NE) in Cohort A and 9.3 ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1040842825003336

Survival outcomes with enfortumab vedotin–containing ... Median overall survival with EV alone was 14.9 months, which increased to 26.7 months with EV+pembrolizumab. •. The objective response rate was 68 % for the ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00762-8/fulltext

2.5-year median follow-up of the phase III EV-302 ... The median OS was 33.8 months (95% CI 26.1-39.3 months) for the EV+P arm and 15.9 months (95% CI 13.6-18.3 months) for the chemotherapy arm (HR ...

4. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-bladder-cancer/158303-asco-gu-2025-clinical-efficacy-of-enfortumab-vedotin-pembrolizumab-in-locally-advanced-or-metastatic-urothelial-carcinoma-a-real-world-retrospective-study.html

ASCO GU 2025: Clinical Efficacy of Enfortumab Vedotin + ... For best overall response, 56 patients (46.6%) experienced partial response, 34 (28.3%) complete response, 12 (10%) progressive disease, 7 (5.8 ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2831221

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 ...

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

EV-302: Updated analysis from the phase 3 global study of ... An exploratory analysis evaluated treatment outcomes and safety in pts with cCR. Results: 886 pts were randomized to receive EV+P (n=442) or ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40795788/

Exploratory subgroup analyses of EV-302: a phase III ... Conclusion: Along with previously published safety data, EV+P demonstrated benefit compared with chemotherapy across all prespecified subgroups, ...

8. 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.