Therapeutic plasma exchange plus enfortumab vedotin and pembrolizumab for bladder and upper urinary tract urothelial cancer
MC220503 Randomized Phase II Rescuing Cancer Immunotherapy With Plasma Exchange in Bladder Cancer 1 (ReCIPE-B1)
This trial will test whether doing a therapeutic plasma exchange before giving enfortumab vedotin (an antibody‑drug conjugate) and pembrolizumab (an immune checkpoint inhibitor) helps people with metastatic or refractory urothelial (bladder or upper tract) cancer who have progressed on prior therapies.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 70 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Mayo Clinic Academic / other |
| Drugs / interventions | enfortumab, pembrolizumab, chemotherapy, Immunotherapy |
| Locations | 1 site (Rochester, Minnesota) |
| Trial ID | NCT07087860 on ClinicalTrials.gov |
What this trial studies
This is a phase II, single‑center trial at Mayo Clinic comparing therapeutic plasma exchange (TPE) followed by re‑challenge with enfortumab vedotin ± pembrolizumab against next‑line standard‑of‑care therapy in patients whose urothelial cancers progressed after prior enfortumab vedotin plus pembrolizumab. TPE is used to remove plasma components before administering the antibody‑drug conjugate and immune checkpoint inhibitor, with the goal of restoring or improving drug activity. The study measures objective response rate by RECIST 1.1 as the primary endpoint and also tracks overall survival, progression‑free survival, duration of response, safety (CTCAE v5.0), and quality of life. A separate cohort will evaluate ADC re‑challenge after prior ADC progression versus historical controls.
Who should consider this trial
Good fit: Adults (≥18 years) with histologically proven metastatic or refractory urothelial carcinoma of the bladder or upper tract with measurable disease, ECOG 0–2, and disease progression after enfortumab vedotin plus pembrolizumab (or ADC progression for the separate cohort) are the intended candidates.
Not a fit: Patients with poor performance status (ECOG >2), inability to undergo plasma exchange or central venous access, uncontrolled medical comorbidities, or active serious infections are unlikely to benefit from participation.
Why it matters
Potential benefit: If successful, this approach could restore sensitivity to enfortumab vedotin ± pembrolizumab and produce higher tumor response rates and potentially longer survival for patients whose urothelial cancers have progressed.
How similar studies have performed: Enfortumab vedotin and pembrolizumab have shown activity in urothelial cancer, but using therapeutic plasma exchange to enable ADC/ICI rechallenge is a novel strategy with little prior clinical evidence.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Rochester, Minnesota
- Mayo Clinic in Rochester — Rochester, Minnesota, United States (Recruiting)
Study contacts
- Principal investigator: Jacob J. Orme, MD, PhD — Mayo Clinic
- Study coordinator: Clinical Trials Referral Office
- Email: mayocliniccancerstudies@mayo.edu
- Phone: 855-776-0015
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.