A Phase 2 interventional study of Best Practice and Biospecimen Collection in Metastatic Bladder Urothelial Carcinoma, Metastatic Renal Pelvis and Ureter Urothelial Carcinoma and Refractory Bladder Urothelial Carcinoma, sponsored by Mayo Clinic. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-08.
Sponsored by Mayo Clinic · Phase 2, Interventional, and Treatment
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.
PRIMARY OBJECTIVES:
I. To compare the response rate (overall response rate [ORR]) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 among patients with metastatic bladder cancer (mBCa) who receive therapeutic plasma exchange (TPE) and antibody drug conjugate/immune checkpoint inhibition (ADC/ICI) re-challenge (group A) versus next-line standard of care therapy (group B) after progression on enfortumab vedotin combined with pembrolizumab (EV/pembro). (ReCIPE-B1 [Groups A and B]) II. To evaluate the response rate (ORR) by RECIST version 1.1 among patients with metastatic bladder cancer (mBCa) who receive therapeutic plasma exchange (TPE) and antibody drug conjugate (ADC) re-challenge (Cohort C) versus historical controls after progression on ADC. (CAKE ReCIPE [Cohort C])
SECONDARY OBJECTIVES:
I. To evaluate and compare the overall survival (OS) of patients receiving TPE and ADC/ICI re-challenge versus next-line standard of care. (ReCIPE-B1 [Groups A and B]) II. To evaluate and compare the duration of response (DOR) by RECIST 1.1 between the arms. (ReCIPE-B1 [Groups A and B]) III. To evaluate and compare progression-free survival (PFS) by RECIST 1.1 between the arms. (ReCIPE-B1 [Groups A and B]) IV. To evaluate safety as assessed per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 in both treatment arms. (ReCIPE-B1 [Groups A and B]) V. To evaluate patients' quality of life (QoL) among both treatment arms as assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy Induced Peripheral Neuropathy 20 (EORTC QLQ-CIPN20) at baseline and every 12 weeks. (ReCIPE-B1 [Groups A and B]) VI. To evaluate the overall survival (OS) of patients receiving TPE and ADC re- challenge. (CAKE ReCIPE [Cohort C]) VII. To evaluate the duration of response (DOR) by RECIST 1.1. (CAKE ReCIPE [Cohort C]) VIII. To evaluate progression-free survival (PFS) by RECIST 1.1. (CAKE ReCIPE [Cohort C]) IX. To evaluate safety as assessed per NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. (CAKE ReCIPE [Cohort C]) X. To evaluate patients' quality of life (QoL) as assessed by EORTC QLQ-CIPN20 at baseline and every 12 weeks. (CAKE ReCIPE [Cohort C])
CORRELATIVE OBJECTIVE:
I. To use circulating exosomes, circulating tumor deoxyribonucleic acid (DNA), and urine tumor DNA for identifying predictive biomarkers of response, progression, or relapse.
OUTLINE: Patients are randomized to 1 of 2 groups. Patients are assigned to Cohort C.
GROUP A: Patients undergo TPE via venous access or central line on days 1-3 of cycles 1-3 and receive enfortumab vedotin intravenously (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 computed tomography (CT), positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI) and collection of blood and urine samples throughout the study. Patients may undergo central line placement prior to TPE.
GROUP B: 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.
COHORT C: 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.
After completion of study treatment, patients are followed up every 6 months for up to 5 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
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
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
Active malignancies (i.e., progressing or requiring treatment change ≤ 24 months before registration) other than the disease being treated under study
EXCEPTIONS:
Localized prostate cancer (T1c/T2N0M0):
History of uncontrolled cardiovascular disease including any of the following ≤ 6 months prior to registration:
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.
Procedure: Biospecimen Collection · Procedure: Central Venous Cannula Insertion · Procedure: Computed Tomography · Drug: Enfortumab Vedotin · Procedure: Magnetic Resonance Imaging · Biological: Pembrolizumab · Procedure: Plasmapheresis · Procedure: Positron Emission Tomography · Other: Questionnaire Administration
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.
Other: Best Practice · Procedure: Biospecimen Collection · Procedure: Magnetic Resonance Imaging · Procedure: Positron Emission Tomography · Other: Questionnaire Administration
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.
Procedure: Biospecimen Collection · Procedure: Central Venous Cannula Insertion · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Procedure: Plasmapheresis · Procedure: Positron Emission Tomography · Other: Questionnaire Administration · Biological: Antibody-Drug Conjugate Therapy
Receive standard of care
Also known as: standard of care, standard therapy
Undergo collection of blood and urine samples
Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo central line placement
Also known as: Central venous catheter, Central Venous Catheter Placement
Undergo CT or PET/CT
Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography
Given IV
Also known as: AGS 22ME, AGS-22M6E, Anti-Nectin 4 ADC ASG-22CE, Anti-nectin-4 Monoclonal Antibody-Drug Conjugate AGS-22M6E, ASG 22CE, ASG-22CE, ASG22CE, Enfortumab Vedotin-ejfv, Padcev
Undergo MRI
Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI
Given IV
Also known as: BCD-201, GME 751, GME751, Keytruda, Lambrolizumab, MK 3475, MK-3475, MK3475, Pembrolizumab Biosimilar BCD-201, Pembrolizumab Biosimilar GME751, Pembrolizumab Biosimilar QL2107, Pembrolizumab Biosimilar RPH-075, Pembrolizumab Biosimilar SB27, QL2107, RPH 075, RPH-075, RPH075, SB 27, SB-27, SB27, SCH 900475, SCH-900475, SCH900475
Undergo TPE
Also known as: Plasma Exchange, Therapeutic Plasma Exchange, Therapeutic Plasmapheresis
Undergo PET/CT
Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT
Ancillary studies
Given IV
Overall response rate (ORR) (Groups A and B)
ORR is defined as proportion of evaluable patients with complete response (CR) or partial response (PR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Time frame: Up to 6 months
ORR (Cohort C)
ORR is defined as proportion of evaluable patients with complete response (CR) or partial response (PR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Time frame: Up to 6 months
Duration of response (DOR) (Groups A and B)
Duration of response is defined as the time from date of objective response (CR or PR) to date of progression per RECIST 1.1 or death due to all causes, whichever occurs first.
Time frame: Up to 5 years
DOR (Cohort C)
Duration of response is defined as the time from date of objective response (CR or PR) to date of progression per RECIST 1.1 or death due to all causes, whichever occurs first.
Time frame: Up to 5 years
Overall survival (OS) (Groups A and B)
OS is defined as the time from the date of randomization to the date of death due to all causes.
Time frame: Up to 5 years
OS (Cohort C)
OS is defined as the time from the date of randomization to the date of death due to all causes.
Time frame: Up to 5 years
Progression-free survival (PFS) (Groups A and B)
PFS is defined as the time from the date of study randomization (assignment to study arm) to the date of death due to all causes or disease progression per RECIST 1.1.
Time frame: Up to 5 years
PFS (Cohort C)
PFS is defined as the time from the date of study randomization (assignment to study arm) to the date of death due to all causes or disease progression per RECIST 1.1.
Time frame: Up to 5 years
Incidence of adverse events (AEs) (Groups A and B)
AEs will be assessed per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: Up to 5 years
Incidence of AEs (Cohort C)
AEs will be assessed per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: Up to 5 years
Quality of life - EORTC QLQ-CIPN20 (Groups A and B)
Quality of life will be measured by change in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Chemotherapy Induced Peripheral Neuropathy 20 (QLQ-CIPN20) scores, a 20-item questionnaire used to assess the severity of neuropathy symptoms experienced by cancer patients during the past week. Questions are answered on a scale of 1-4 where 1=not at all, 2= a little, 3=quite a bit, and 4=very much. Higher scores indicate greater severity of symptoms.
Time frame: Baseline; every 12 weeks (every 4 cycles) until treatment completion, up to 5 years
Quality of life - EORTC QLQ-CIPN20 (Cohort C)
Quality of life will be measured by change in EORTC QLQ-CIPN20 scores, a 20-item questionnaire used to assess the severity of neuropathy symptoms experienced by cancer patients during the past week. Questions are answered on a scale of 1-4 where 1=not at all, 2= a little, 3=quite a bit, and 4=very much. Higher scores indicate greater severity of symptoms.
Time frame: Baseline; every 12 weeks (every 4 cycles) until treatment completion, up to 5 years
Plan to share: No
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