Therapeutic Plasma Exchange with Enfortumab Vedotin and Pembrolizumab for Bladder Cancer

(RECIPE-B1 Trial)

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Disqualifiers: Pregnancy, Active malignancies, Cardiovascular, 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: 27

Duration: Up to 6 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for individuals with bladder or upper urinary tract cancer that has spread and not responded to previous treatments. Researchers are testing whether combining therapeutic plasma exchange (a method to filter the blood) with two cancer drugs, enfortumab vedotin and pembrolizumab, proves more effective than standard treatments. This trial targets patients whose cancer has worsened despite prior treatment with enfortumab vedotin and pembrolizumab. Participants will either receive the new combination treatment or continue with the usual care options provided by their doctor. This study may suit those with metastatic bladder cancer who have experienced cancer progression despite prior treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that using enfortumab vedotin and pembrolizumab together is generally safe. In studies comparing these drugs to standard chemotherapy for bladder cancer, patients lived longer and experienced manageable side effects. Most side effects were mild, such as tiredness, hair loss, and changes in taste. The FDA has already approved these drugs for treating bladder cancer, indicating their safety for patients.

Therapeutic plasma exchange (TPE) is less common but serves as a standard method to filter blood in certain treatments. While TPE is usually safe, some individuals might feel dizzy or tired during the process.

Overall, the combination of enfortumab vedotin, pembrolizumab, and TPE appears well-tolerated based on current research, although ongoing studies continue to investigate this further. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of enfortumab vedotin and pembrolizumab for bladder cancer because it offers a unique dual approach. Unlike standard treatments like chemotherapy or radiation, enfortumab vedotin is an antibody-drug conjugate that specifically targets cancer cells by delivering a potent chemotherapy agent directly to them, minimizing damage to healthy cells. Pembrolizumab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. This combination aims to enhance the body's natural defenses while directly attacking the cancer, potentially offering a more effective and less toxic treatment option.

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

Research has shown that combining enfortumab vedotin with pembrolizumab may effectively treat advanced bladder cancer. Studies have found that this combination can significantly extend patient survival, with one study showing an average survival of 26.7 months compared to 14.9 months with enfortumab alone. The treatment also achieved an objective response rate of about 68%, indicating that the cancer shrank or disappeared in many cases. In this trial, participants in Group A will receive therapeutic plasma exchange (TPE) alongside enfortumab vedotin and pembrolizumab to determine if TPE can enhance the effectiveness of these drugs. Overall, the evidence for using enfortumab vedotin and pembrolizumab is promising for individuals with advanced bladder cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

Jacob J. Orme, MD, PhD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Adults with bladder or upper urinary tract cancers that have spread and are unresponsive to previous treatments. Participants must be over 18, have a certain level of physical fitness (ECOG grade 0-2), adequate blood counts, not pregnant if applicable, and sufficient kidney function. They should also have specific levels of liver enzymes within an acceptable range.

Inclusion Criteria

My hemoglobin level is above 7.0 g/dL.

My platelet count is at least 75,000 and was checked within the last month.

My liver tests are within the required limits.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo therapeutic plasma exchange and receive enfortumab vedotin and pembrolizumab. Cycles repeat every 21 days.

Up to 6 months

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 5 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Enfortumab Vedotin
• Pembrolizumab
• Plasmapheresis

Trial Overview This phase II trial is testing whether therapeutic plasma exchange followed by enfortumab vedotin and pembrolizumab improves outcomes compared to standard care for metastatic, treatment-resistant bladder cancer. TPE removes and replaces plasma in the blood; enfortumab vedotin targets cancer cells with nectin-4 protein; pembrolizumab boosts the immune system's response against cancer.

How Is the Trial Designed?

Group I: Group A (TPE, EV, pembrolizumab) Experimental Treatment 9 Interventions

Patients undergo TPE via venous access or central line on days 1-3 of cycles 1-3 and receive enfortumab vedotin IV over 30 minutes and pembrolizumab IV over 30 minutes on day 3 of cycles 1-3 and day 1 of cycles 4 and beyond. Cycles repeat every 21 days in the absence of disease progression of unacceptable toxicity. Patients also undergo CT, PET/CT, or MRI and collection of blood and urine samples throughout the study. Patients may undergo central line placement prior to TPE.

Group II: Group B (standard of care) Active Control 5 Interventions

Patients receive physician's choice of standard of care next-line therapy. Patients also undergo CT, PET/CT, or MRI and collection of blood and urine samples throughout the study.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

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.