Pembrolizumab for Bladder Cancer

Overseen By Lead Onco Nurse

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Oklahoma

Must not be taking: Antimicrobials, PD-(L)-1 inhibitors

Disqualifiers: Uncontrolled diabetes, CNS metastases, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether pembrolizumab, a cancer-fighting drug, can effectively treat bladder cancer that has spread to other parts of the body. Initially, patients receive a combination of pembrolizumab and another drug, Enfortumab Vedotin (an antibody-drug conjugate), and continue with pembrolizumab alone if they show improvement. The goal is to determine if this approach can maintain or improve the patient's condition without additional side effects. Individuals with advanced bladder cancer who haven't previously received certain treatments may be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to important advancements in cancer care.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the trial team to ensure they don't interfere with the study.

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

Research has shown that pembrolizumab, when used alone, is generally well-tolerated by patients with advanced bladder cancer. It can extend patients' lives and causes fewer side effects than traditional chemotherapy. The most common side effects include tiredness and itching, while serious reactions are rare.

Studies have also indicated that enfortumab vedotin is effective and safe for individuals with advanced bladder cancer. It can prolong life and has a good response rate. Common side effects include skin reactions and nerve issues, which can be managed.

Both treatments have been studied separately and together, demonstrating promising results in managing advanced bladder cancers with a reasonable safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about pembrolizumab for bladder cancer because it offers a new approach for patients with metastatic urothelial carcinoma. Unlike standard treatments that primarily rely on chemotherapy, pembrolizumab is an immunotherapy that harnesses the body's immune system to fight cancer cells. This treatment is particularly promising because it can be used in a de-escalation strategy, transitioning from a combination therapy with enfortumab vedotin to pembrolizumab alone if patients respond well. This approach aims to maintain effectiveness while potentially reducing side effects, offering hope for better outcomes with fewer challenges for patients.

What evidence suggests that pembrolizumab might be an effective treatment for metastatic urothelial cancer?

Research has shown that using pembrolizumab with enfortumab vedotin, which participants in this trial will receive as part of the Pembrolizumab & Enfortumab Vedotin (PEV) treatment arm, holds promise for treating advanced bladder cancer. One study found that patients taking this combination lived an average of 33.8 months, significantly longer than the 15.9 months for those who received standard chemotherapy. Additionally, 68% of patients experienced a reduction or disappearance of their cancer with this treatment. These findings suggest that pembrolizumab and enfortumab vedotin may be more effective than traditional chemotherapy for this cancer. ^{5 6 7 8 9}

Who Is on the Research Team?

Adanma Ayanambakkam, MD

Principal Investigator

University of Oklahoma

Are You a Good Fit for This Trial?

This trial is for patients with metastatic urothelial cancer who have already undergone 24 weeks of initial treatment with pembrolizumab & Enfortumab Vedotin (PEV). Specific eligibility criteria are not provided, but typically include factors like age, overall health, and the stage of cancer.

Inclusion Criteria

Measurable disease according to the New Response Evaluation Criteria in Solid Tumors (RECIST v1.1)

My doctor thinks I can be treated with cisplatin or carboplatin.

My cancer is advanced and cannot be removed by surgery.

Exclusion Criteria

Has a history of autoimmune disease that has required systemic immunosuppressive treatment in the past 2 years, or uncontrolled autoimmune disease

Patient's estimated life expectancy is less than 12 weeks

Known severe (≥ Grade 3) hypersensitivity to any EV excipient contained in the drug formulation of EV

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive first-line PEV therapy for 24 weeks, followed by assessment for disease progression and ctDNA reduction

24 weeks

De-escalation

Participants transition to pembrolizumab monotherapy if stable disease or response is observed, with ongoing monitoring for progression or toxicity

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for progression-free survival and adverse events

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Enfortumab Vedotin
• Pembrolizumab

Trial Overview The study tests if pembrolizumab alone can maintain or improve the response in mUC patients after they've received a combination of pembrolizumab and Enfortumab Vedotin. It involves an initial phase with both drugs followed by a de-escalation to just pembrolizumab.

How Is the Trial Designed?

Group I: Pembrolizumab & Enfortumab Vedotin (PEV) Experimental Treatment 2 Interventions

Patients with metastatic urothelial carcinoma (mUC) will initiate first-line (1L) PEV therapy as the standard of care. At 24 weeks, radiographic imaging will be performed to evaluate disease status. Patients who exhibit either stable disease or ongoing radiographic response, accompanied by a ≥50% reduction in circulating tumor DNA (ctDNA) levels, will transition to pembrolizumab monotherapy as part of a treatment de-escalation strategy. Pembrolizumab will be continued until the occurrence of disease progression or unacceptable toxicity. In the event of progression or intolerance, patients will be re-challenged with first-line PEV therapy and continue treatment until completion of the study-defined treatment period.

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Natera, Inc.

Industry Sponsor

Trials

56

Recruited

50,700+

Citations

1. 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 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38446675/

Enfortumab Vedotin and Pembrolizumab in Untreated ... Treatment with enfortumab vedotin and pembrolizumab resulted in significantly better outcomes than chemotherapy in patients with untreated locally advanced or ...

3. 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.

4. 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 ...

5. 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 ...

6. 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.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10535083/

Enfortumab vedotin in metastatic urothelial carcinoma EV has been approved as a single agent for pre-treated mUC, with interesting improvements in response rate and survival in a setting with limited treatment ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.553

Safety and efficacy of enfortumab vedotin in patients with ... Overall response rate (ORR) was 46.3% (partial remission: 42.0%, complete response 4.3%), disease control rate was 58.0%. Median OS (mOS) was ...

9. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-bladder-cancer/158279-asco-gu-2025-real-world-analysis-of-the-efficacy-and-safety-of-enfortumab-vedotin-in-patients-with-locally-advanced-or-metastatic-urothelial-carcinoma-a-multicenter-retrospective-study.html

ASCO GU 2025: Real-World Analysis of the Efficacy and ... ASCO GU 2025 efficacy and safety of enfortumab vedotin (EV) in patients with locally advanced or metastatic urothelial carcinoma.