Recruiting
Phase 2

TPE & Enfortumab Vedotin & Pembrolizumab

Sponsor:

Mayo Clinic

Code:

NCT07087860

Conditions

Metastatic Bladder Urothelial Carcinoma

Metastatic Renal Pelvis and Ureter Urothelial Carcinoma

Refractory Bladder Urothelial Carcinoma

Refractory Renal Pelvis and Ureter Urothelial Carcinoma

Stage IV Bladder Cancer AJCC v7

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Best Practice

Biospecimen Collection

Central Venous Cannula Insertion

Computed Tomography

Enfortumab Vedotin

Study Details

Brief summary:

This phase II trial compares therapeutic plasma exchange followed by enfortumab vedotin and pembrolizumab to standard of care next-line therapy for the treatment of patients with bladder or upper urinary tract cancers that have spread from where they first started (primary site) to other places in the body (metastatic) and that have not responded to previous treatment (refractory). TPE is a process that slowly removes a patient's blood through an intravenous or central line. The blood is sent through a machine that separates the plasma (the liquid part of blood) from other blood components (red cells, white cells, platelets). The plasma is then removed. The remaining blood components are combined with replacement fluid and returned to the patient's bloodstream through the intravenous or central line. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of cancer cells. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Treatment with enfortumab vedotin and pembrolizumab is already approved by the Food and Drug Administration for the treatment of bladder cancer, but TPE is not. Combining TPE with enfortumab vedotin and pembrolizumab may work better than standard of care options for treating metastatic and refractory bladder and urinary tract cancers. This study also evaluates the effect of TPE with standard of care antibody drug conjugates (ADCs) in treating patients with refractory metastatic bladder cancer. ADC therapy is treatment with a monoclonal antibody linked to a chemotherapy drug. It is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of tumor cells, and delivers chemotherapy to kill them. Giving TPE with standard of care ADC therapy may be effective in treating patients with refractory metastatic bladder cancer.

Conditions

Metastatic Bladder Urothelial Carcinoma

Metastatic Renal Pelvis and Ureter Urothelial Carcinoma

Refractory Bladder Urothelial Carcinoma

Refractory Renal Pelvis and Ureter Urothelial Carcinoma

Stage IV Bladder Cancer AJCC v7

Study ID

NCT07087860

Start date

Aug 1, 2025

Status verified date

May, 2026

Completion date

Aug 7, 2028

Anticipated

Primary completion date

Aug 7, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Age ≥ 18 years
  • GROPUS A and B (reCIPE-B1): Histologically proven urothelial carcinoma \[American Joint Committee on Cancer (AJCC) 2017\] of the bladder (BCa) or upper urothelial tract (UTUC), that has progressed despite enfortumab vedotin and pembrolizumab treatment

  • NOTE: Primary or secondary progression are allowed, therapies are not required to be concurrent or immediately antecedent to enrollment)
  • COHORT C (CAKE ReCIPE): Histologically proven urothelial carcinoma (AJCC 2017) of the bladder (BCa) or upper urothelial tract (UTUC), that has progressed despite ADC AND is otherwise not a candidate for Groups A and B

  • NOTE: Patients in Groups A and B who have progressed on that treatment are candidates for this cohort. Such patients must be re-consented and re- enrolled
  • Measurable disease per RECIST version (v)1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status grade 0, 1, or 2
  • Hemoglobin > 7.0 g/dL (obtained ≤ 30 days prior to registration)
  • Platelet count ≥ 75,000/mm\^3 (obtained ≤ 30 days prior to registration)
  • Alanine aminotransferase (ALT) OR aspartate transaminase (AST) ≤ 3.5 x upper limit of normal (ULN) OR total bilirubin ≤ 3 x ULN OR direct bilirubin ≤ 3 x ULN (obtained ≤ 30 days prior to registration)
  • Estimated glomerular filtration rate (GFR) ≥ 15 ml/min (obtained ≤ 30 days prior to registration)
  • Negative pregnancy test ≤ 8 days prior to registration, for persons of childbearing potential only
  • Provide written informed consent
  • Ability to complete questionnaire(s) by themselves or with assistance
  • Willingness to undergo treatment as assigned (group A: TPE + EV/pembro; OR group B: next line standard of care; OR Cohort C TPE + ADC)
  • Willingness to provide mandatory blood and fluid specimens for correlative research
  • Willingness to provide tissue specimens for correlative research
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

Exclusion Criteria:

  • Any of the following because this study involves an investigational agent, the genotoxic, mutagenic, and teratogenic effects of which on the developing fetus and newborn are unknown

  • Pregnant persons
  • Nursing persons
  • Persons of childbearing potential or able to father a child who are unwilling to employ adequate contraception
  • Any of the following histologic variants/divergent differentiation: Any amount of neuroendocrine or signet ring cell features
  • Active malignancies (i.e., progressing or requiring treatment change ≤ 24 months before registration) other than the disease being treated under study

  • EXCEPTIONS:

  • Skin cancer (melanoma or non-melanoma) that is considered completely cured
  • Non-invasive cervical cancer that is considered completely cured
  • Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ considered to have a very low risk of recurrence
  • Localized prostate cancer (T1c/T2N0M0):

  • Gleason score 6, treated by either surgery or ablation ≤ 24 months prior to registration or untreated and under active surveillance
  • Gleason score 3+4 that has been treated (may include surgery or ablation) ≤ 24 months prior to registration and considered to have a very low risk of recurrence (i.e., cT1c or pT2 on prostatectomy specimen)
  • History of uncontrolled cardiovascular disease including any of the following ≤ 6 months prior to registration:

  • Significant cardiovascular disease \[New York Heart Association (NYHA) class ≥ III\], symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction, ventricular fibrillation, Torsades de Pointes, cerebrovascular accident, or transient ischemic attack
  • Psychiatric illness/social situations (e.g., substance abuse) that would limit compliance with study requirements
  • Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participants (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

Study Design

Enrollment

70 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Group A (TPE, EV, pembrolizumab)

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 on days 3 and 10 of cycles 1-3 and on days 1 and 8 of cycle 4 and beyond 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.

active comparator: Group B (standard of care)

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.

experimental: Cohort C (TPE, ADC)

Patients undergo TPE via venous access or central line on days 1-3 of cycles 1-3 only and receive physician's choice of standard of care ADC IV on day 3 of cycles 1-3 and on day 1 of cycles 4 and beyond. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, PET/CT, or MRI and collection of blood and urine samples throughout the study.

Interventions

Best Practice

Receive standard of care

Biospecimen Collection

Undergo collection of blood and urine samples

Central Venous Cannula Insertion

Undergo central line placement

Computed Tomography

Undergo CT or PET/CT

Enfortumab Vedotin

Given IV

Magnetic Resonance Imaging

Undergo MRI

Pembrolizumab

Given IV

Plasmapheresis

Undergo TPE

Positron Emission Tomography

Undergo PET/CT

Questionnaire Administration

Ancillary studies

Antibody-Drug Conjugate Therapy

Given IV

Primary outcome measure

  • Overall response rate (ORR) (Groups A and B) [ Time Frame: Up to 6 months ]
  • ORR (Cohort C) [ Time Frame: Up to 6 months ]

Central Contacts and Locations

Central contacts

Clinical Trials Referral Office

855-776-0015mayocliniccancerstudies@mayo.edu

Locations

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Clinical Trials Referral Office

855-776-0015mayocliniccancerstudies@mayo.edu

Principal Investigator:

Jacob J. Orme, MD, PhD

More Information

Sponsor

Mayo Clinic

Last update posted

May 8, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Mayo Clinic on 2026-05-08.