RecruitingUrothelial Carcinoma
Study of Neoadjuvant Enfortumab Vedotin and Pembrolizumab in Upper Tract Urothelial Cancer
Eligible age
18+ yrs
Accepts
All genders
Locations
2 states
Healthy volunteers
No
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About this study
This trial is a multi-site, single-arm, phase 2 trial of neoadjuvant combination of enfortumab vedotin and pembrolizumab in patients with high-grade localized/locally advanced cT1-4 N0-1 M0 upper tract urothelial cancer who are deemed eligible for curative-intent surgery (radical nephroureterectomy or distal ureterectomy) followed by adjuvant pembrolizumab.
Sponsor: University of Michigan Rogel Cancer Center
You may qualify if…
- ✓ Patients must have a diagnosis of high-grade upper tract (renal pelvis and/or ureter) urothelial carcinoma proven by biopsy or cytology within 60 days prior to registration with the following (cT1-4 N0-1 M0): a. Upper urinary tract mass on cross-sectional imaging or Tumor directly visualized during upper urinary tract endoscopy before referral to medical oncology. b. No regional lymph node metastasis, a single regional lymph node metastasis, or multiple regional lymph node metastases (no distant lymph node metastases)
- ✓ Patients must not have any component of small cell carcinoma. Other variant histologic types are permitted provided the predominant (≥50%) subtype is urothelial carcinoma.
- ✓ Patients must be considered to be a candidate for definitive surgery (nephroureterectomy or distal ureterectomy) with curative intent by the treating urologist. Lymph node dissection is strongly encouraged but its scope and determination will be at the discretion of the treating urologist. Details of the surgery such as bladder cuff removal are left to the discretion of the treating urologist. Robotic or open approaches are allowed.
- ✓ Prior local endoscopic therapy for upper tract urothelial cancer is permitted if completed at least 6 months prior to the initiation of study treatment and if all toxicities from such therapy have improved to grade 1 or resolved.
- ✓ Prior uro-oncologic history: a. History of or active non-invasive carcinoma or carcinoma in situ of the bladder/urethra or upper tract is allowed. b. Patients may have received prior intravesical chemotherapy or immunotherapy such as BCG. c. Prior neoadjuvant or adjuvant chemotherapy or antibody-drug conjugate for bladder cancer or invasive contralateral upper tract cancer is allowed but must have been completed ≥ 1 year prior to study registration.
- ✓ Patients must be age ≥ 18 on the date of registration.
- ✓ ECOG Performance Status 0-1.
- ✓ Criteria for patients with hepatitis B or C are listed below. Hepatitis B and C screening tests are not required unless there is a known history of HBV or HCV infection or as mandated by local healthy authority. Hepatitis B positive subjects • Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to enrollment. • Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening. • Participants must have completed curative anti-viral therapy at least 4 weeks prior to enrollment.
You may not qualify if…
- ✕ Prior exposure to immune-mediated therapy, including but not limited to, other anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4), anti-PD1, anti-PD-L1, anti-PD-L2 antibodies, and therapeutic anticancer vaccines.
- ✕ Prior exposure to monomethyl auristatin E antibody-drug conjugates (MMAE ADC).
- ✕ Patient is currently on or used immunosuppressive medication within 14 days prior to the first dose of pembrolizumab. The following are exceptions to this criterion: o Intranasal, inhaled, intra-auricular, topical steroids, or local steroid injections (e.g., intra-articular injection). o Use of chronic immunosuppressive agents at baseline at doses not to exceed more than prednisone 10 mg/day or equivalent. o Steroids as premedications for hypersensitivity reactions (e.g., CT scan premedication).
- ✕ Active or prior documented autoimmune or inflammatory disorders requiring immunosuppressive therapy within 2 years prior to registration. Exceptions are well-controlled hyper/hypothyroidism, celiac disease controlled by diet alone, diabetes mellitus type 1, alopecia, psoriasis, eczema, lichen planus, vitiligo, or similar skin/mucosa conditions.
- ✕ Evidence of metastasis (M1) on axial imaging at baseline.
- ✕ History of invasive, node positive, or metastatic bladder cancer OR invasive contralateral upper tract cancer within 2 years prior to registration.
- ✕ Enrolled in another interventional clinical trial at the time of registration.
- ✕ Patient has another active malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 1 year. The time requirement does not apply to participants who underwent successful definitive resection of non-melanoma skin cancers, superficial bladder cancer (described above in inclusion criteria 6), in situ cervical cancer, other in situ cancers, or either clinically insignificant per the investigator (e.g., ≤Gleason 3+4) on surveillance or previously treated prostate cancer without rising PSA and no plan to treat. NOTE: Patients with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
Where it's recruiting
Michigan
Ann Arbor
Pennsylvania
Philadelphia
Source: ClinicalTrials.gov · NCT06356155 · last updated 2026-07-16