A Phase 2 Study Evaluating Bladder Preservation With Enfortumab Vedotin Plus Pembrolizumab in Patients With Muscle-Invasive Urothelial Cancer

NCT07822373 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCI205161
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate whether Enfortumab Vedotin in combination with Pembrolizumab can achieve a clinical response that preserves the bladder and avoids the need for cystectomy or radiation therapy in patients with urothelial cancer.

Conditions

Muscle-invasive Bladder Urothelial Carcinoma

Outcome Measures

Primary Outcomes (4)

• cT0 or cTa low-grade disease as assessed by cystoscopy and bladder biopsy, including all visually abnormal sites in addition to reTURBT or biopsy of the known site of MIBC before neo- adjuvant therapy

  To assess the proportion of patients who have achieved a clinical complete response and have maintained bladder preservation without undergoing definitive treatment of cystectomy or radiation after 4 cycles of study treatment.

  6 years

• Negative tumor-informed ctDNA

  To assess the proportion of patients who have achieved a clinical complete response and have maintained bladder preservation without undergoing definitive treatment of cystectomy or radiation after 4 cycles of study treatment.

  6 years

• The absence of malignant cells on urine cytology

  To assess the proportion of patients who have achieved a clinical complete response and have maintained bladder preservation without undergoing definitive treatment of cystectomy or radiation after 4 cycles of study treatment.

  6 years

• No definitive evidence of new local or metastatic disease at cross-sectional imaging per investigator judgement

  To assess the proportion of patients who have achieved a clinical complete response and have maintained bladder preservation without undergoing definitive treatment of cystectomy or radiation after 4 cycles of study treatment.

  6 years

Secondary Outcomes (13)

• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type.

  6 years

• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by severity (as defined by the NIH CTCAE, version 6.0).

  6 years

• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by seriousness.

  6 years

• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by duration.

  6 years

• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by their relationship to the study treatment.

  6 years

Study Arms (1)

Treatment: All Patients

EXPERIMENTAL

All patients will be treated with enfortumab vedotin in combination with pembrolizumab.

Drug: Enfortumab vedotin; Drug: Pembrolizumab

Interventions

Enfortumab vedotin DRUG

Enfortumab vedotin 1.25 mg/kg, IV on days 1 and 8 on a 21day cycle for 9 cycles

Treatment: All Patients

Pembrolizumab DRUG

Subjects will receive one year of treatment with pembrolizumab IV or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) SC. Treatment will be administered per institutional standards every 3 weeks or 6 weeks, at the physician's discretion.

Treatment: All Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant aged ≥ 18 years.
• Disease criteria:
• Histologically confirmed muscle-invasive urothelial carcinoma (T2-T3N0M0) without small cell variant histology of bladder. Other variant histologies are allowed if urothelial histology is present.
• No evidence of local or distant metastasis on CT scans.
• Urothelial carcinomas not originating from the bladder (eg, upper tract \[ureters, renal pelvis\], urethra) are not eligible.
• Eligible to receive enfortumab vedotin and pembrolizumab.
• ECOG Performance Status ≤ 2.
• Adequate organ function as defined as:
• Hematologic:
• Absolute neutrophil count ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 10 g/dL
• Hepatic:
• Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN), ≤3× ULN for subjects with suspected Gilbert's syndrome with direct bilirubin ≤ ULN.
• AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN

You may not qualify if:

• Prior systemic therapy for urothelial cancer.
• Receiving other systemic investigational agents for urothelial cancer.
• Hemoglobin A1c \> 8% or 7-8% with associated diabetes symptoms.
• Autoimmune disease requiring systemic steroids or immunosuppressive agents in the last 2 years.
• Neuropathy Grade ≥2.
• Prior radiotherapy for urothelial cancer.
• Major surgery within 4 weeks prior to starting study therapy or participant has not fully recovered from major surgery per clinical investigator.
• The diagnosis of another malignancy which, in the opinion of the Investigator, is likely to negatively impact study objectives or the participant's safety or ability to participate in the study.
• Known metastatic disease.
• Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias per clinical investigator.
• Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other significant ischemic events per clinical investigator, within 3 months before the first dose. Subjects with pulmonary embolism or deep vein thrombosis if adequately managed can be enrolled.
• Any other condition that would, in the Investigator's judgment, contraindicate the participant's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, social/ psychological issues, etc.)
• Active infection expected to interfere with study treatment in the opinion of the investigator.

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Interventions

enfortumab vedotin; pembrolizumab

Central Study Contacts

Kristen Jewkes

CONTACT

801-585-1753; Kristen.Jewkes@hci.utah.edu

Umang Swami, MD

CONTACT

801-585-0255; Umang.Swami@hci.utah.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2026
• First Posted: September 16, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2034
• Study Completion (Estimated): November 1, 2035
• Last Updated: September 16, 2026

Record last verified: 2026-09

Locations

US (1)