Enfortumab Vedotin Plus Pembrolizumab With Selective Bladder Sparing for Treatment of Muscle-invasive Bladder Cancer

NCT06809140 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN-GU22-598
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 5

Brief Summary

Patients with MIBC will receive 3 cycles (C1-C3) of induction enfortumab vedotin plus pembrolizumab followed by restaging including MRI of the bladder, urine cytology, and cystoscopy with TURBT of any visible tumor and/or resection site plus random biopsies using a recommended template. Patients achieving a stringently defined cCR (clinical complete response) will receive 14 cycles of "maintenance" treatment. Enfortumab vedotin will be administered during the first 6 cycles (C4-C9) of "maintenance" treatment and pembrolizumab will be given all 14 cycles (C4-C14). Patients with any residual disease at clinical restaging (i.e., \>cTa disease) will undergo cystectomy.

Conditions

Muscle Invasive Bladder Urothelial Carcinoma

Keywords

MIBC; Pembrolizumab; Enfortumab vedotin

Outcome Measures

Primary Outcomes (1)

• Complete response rate with enfortumab vedotin plus pembrolizumab for MIBC

  Clinical complete response rate will be defined as cT0 or cTa (low grade) disease at the time of restaging after 3 cycles of induction enfortumab vedotin plus pembrolizumab

  9 weeks

Secondary Outcomes (12)

• Safety of enfortumab vedotin plus pembrolizumab

  2 years

• Positive predictive value (PPV) of cCR Patients

  2 years

• Positive predictive value (PPV) of cCR Patients

  2 years

• Local recurrence-free survival

  4 years

• Association between clinical complete response (cCR) and bladder-intact event-free survival

  4 years

Study Arms (1)

Enfortumab vedotin plus pembrolizumab

EXPERIMENTAL

Patients with MIBC will receive 3 cycles (C1-C3) of induction enfortumab vedotin (1.25 mg/kg for a maximum dose of 125 mg) plus pembrolizumab (200 mg) followed by restaging including MRI of the bladder, urine cytology, and cystoscopy with TURBT of any visible tumor and/or resection site plus random biopsies using a recommended template. Patients achieving a stringently defined cCR (defined below) will receive 14 cycles of "maintenance" treatment. Enfortumab vedotin (1.25 mg/kg for a maximum dose of 125 mg) will be administered during the first 6 cycles (C4-C9) of "maintenance" treatment and pembrolizumab (200 mg) will be given all 14 cycles (C4-C14). Patients with any residual disease at clinical restaging (i.e., \>cTa disease) will undergo cystectomy.

Drug: Enfortumab vedotin; Drug: Pembrolizumab

Interventions

Enfortumab vedotin DRUG

1.25 mg/kg (maximum dose 125 mg)

Enfortumab vedotin plus pembrolizumab

Pembrolizumab DRUG

200 mg

Enfortumab vedotin plus pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-1 within 28 days prior to registration.
• Histological evidence of clinically localized muscle-invasive urothelial cancer of the bladder clinical stage T2-3N0M0. Participants with mixed histology are eligible provided the urothelial component is ≥50% with the following exceptions: (a) tumors with any degree of squamous differentiation are eligible provided there is a urothelial cancer component, (b) tumors that contain any component of neuroendocrine histology are not eligible. N0 will be considered as the absence of radiographically enlarged lymph nodes on baseline imaging (i.e., Patients with lymph nodes ≥1 cm in short axis on imaging are not eligible).
• Have undergone a standard of care maximal transurethral resection of bladder tumor ≤ 90 days prior C1D1. A maximal TURBT should be performed when feasible and is defined as a macroscopically complete resection of bladder tumor.
• All subjects must have adequate transurethral resection of bladder tumor tissue available for submission identified during screening. The specimen must include tumor tissue (i.e., if a restaging maximal TURBT was performed and there was no cancer in the specimen, tissue from the most recent prior TURBT that established the diagnosis of muscle-invasive urothelial cancer of the bladder should be submitted). Tissue from both the restaging TURBT and the prior diagnostic TURBT may be requested. Subjects without available archival tissue must be discussed with the sponsor-investigator.
• Be deemed eligible to undergo radical cystectomy and pelvic lymph node dissection
• Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration.
• Absolute neutrophil count (ANC): ≥ 1.5 x 10\^9/L
• Hemoglobin (Hgb): ≥ 9 g/dL
• Platelets: ≥ 100 x 10\^9/L
• Creatinine clearance: ≥ 30 mL/min
• Bilirubin: ≤ 1.5 ×ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 × ULN
• Aspartate aminotransferase (AST): ≤ 2.5 × ULN
• Alanine aminotransferase (ALT): ≤ 2.5 × ULN

You may not qualify if:

• Pre-existing sensory or motor neuropathy Grade ≥ 2
• Ongoing clinically significant toxicity (Grade 2 or higher with the exception of alopecia) associated with prior treatment (including systemic therapy, radiotherapy or surgery).
• Prior systemic chemotherapy for muscle-invasive urothelial cancer of the bladder.
• Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured. Patients with intermediate or lower risk prostate cancer as defined by the National Comprehensive Cancer Network (NCCN) risk stratification guidelines may be eligible for enrollment.
• Prior radiation therapy for bladder cancer.
• Hemoglobin A1c ≥ 8% or hemoglobin A1c 7%-\<8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained
• Active infection requiring systemic therapy.
• Known active Hepatitis B or C infection. NOTE: Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• HIV-infected patients on effective anti-retroviral therapy with an undetectable viral load are eligible.
• Has a known history of active TB (Bacillus Tuberculosis).
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has severe hypersensitivity (≥ Grade 3) to pembrolizumab or enfortumab vedotin and/or any of their excipients.

Sponsors & Collaborators

• Matthew Galsky: lead
• Seagen Inc.: collaborator
• Astellas Pharma Inc: collaborator
• Merck Sharp & Dohme LLC: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (5)

City of Hope

Duarte, California, 91010, United States

RECRUITING

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

RECRUITING

MeSH Terms

Interventions

enfortumab vedotin; pembrolizumab

Study Officials

• Matthew Galsky, MD

  Sponsor-Investigator

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthew Galsky, MD

CONTACT

212-659-5452; matthew.galsky@mssm.edu

Ahran Lee

CONTACT

317-634-5842; alee@hoosiercancer.org

Study Design

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

Model Details: Patients with MIBC will receive 3 cycles (C1-C3) of induction enfortumab vedotin plus pembrolizumab followed by restaging including MRI of the bladder, urine cytology, and cystoscopy with TURBT of any visible tumor and/or resection site plus random biopsies using a recommended template. Patients achieving a stringently defined cCR will receive 14 cycles of "maintenance" treatment. Enfortumab vedotin will be administered during the first 6 cycles (C4-C9) of "maintenance" treatment and pembrolizumab will be given all 14 cycles (C4-C14). Patients with any residual disease at clinical restaging (i.e., \>cTa disease) will undergo cystectomy.

Study Record Dates

• First Submitted: January 17, 2025
• First Posted: February 5, 2025
• Study Start: April 7, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2029
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)