Enfortumab Vedotin and Pembrolizumab Combined With Radiotherapy in Muscle Invasive Bladder Cancer

Part of paid clinical trials in San Francisco, California.

Sponsor
University of California, San Francisco
Study ID
NCT06470282
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Bladder Cancer
  • Muscle-Invasive Bladder Carcinoma
  • Stage II Bladder Cancer AJCC v8
  • Stage IIIA Bladder Cancer AJCC v8

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Enfortumab Vedotin — DRUG
    Given intravenously (IV)
  • Pembrolizumab — BIOLOGICAL
    Given IV
  • Intensity Modulated Radiation Therapy (IMRT) — RADIATION
    Undergo standard of care, IMRT
  • Transurethral Resection of Bladder Tumor — PROCEDURE
    Undergo TURBT
  • Cystoscopy (CS) — PROCEDURE
    Undergo cystoscopy
  • Computed Tomography (CT) — PROCEDURE
    Undergo CT imaging
  • Magnetic Resonance Imaging (MRI) — PROCEDURE
    Undergo MRI imaging
  • Positron Emission Tomography (PET) — PROCEDURE
    Undergo PET Scan, may be combined with CT (PET/CT)

Study Details

This phase Ib/II trial studies the side effects, best dose, and effectiveness of enfortumab vedotin (EV) in combination with pembrolizumab and radiation therapy for treating patients with muscle invasive bladder cancer. Standard of care treatment for muscle invasive bladder cancer is chemotherapy, to shrink the tumor before the main treatment is given (neoadjuvant), followed by surgery to remove all of the bladder as well as nearby tissues and organs (radical cystectomy). In cases where patients are not candidates for the standard of care approach or prefer a bladder sparing option, tri-modality therapy with transurethral resection of bladder tumor (TURBT) followed by combined chemotherapy and radiation therapy is used. 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 tumor cells. Enfortumab attaches to a protein called nectin-4 on tumor 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. Intensity-modulated radiation therapy is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Giving enfortumab vedotin with pembrolizumab and radiation therapy may work better in treating patients with muscle invasive bladder cancer.

Key Dates

Start date
Mar 31, 2025
Status verified
Feb 2026
Primary completion
Jan 31, 2028
Completion
Jan 31, 2028

Study Design

Enrollment
47 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Dose Level 1: 0.75 mg/kg Enfortumab Vedotin (Starting Dose)
    Participants receive 0.75 mg/kg enfortumab vedotin intravenously (IV) over 30 minutes on days 1 and 8 of cycles 1-5 and pembrolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 5 cycles of enfortumab vedotin and up to 17 cycles of pembrolizumab in the absence of disease progression or unacceptable toxicity. Beginning on cycle 1 day 1, participants also undergo standard of care intensity modulated radiation therapy (IMRT) once daily (QD) for 32 days over 6.5-8 weeks. Participants also undergo TURBT, cystoscopy, as well as imaging throughout the study.
  • Experimental: Dose Level 2: 1.0 mg/kg Enfortumab Vedotin
    Participants receive 1.05 mg/kg enfortumab vedotin intravenously (IV) over 30 minutes on days 1 and 8 of cycles 1-5 and pembrolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 5 cycles of enfortumab vedotin and up to 17 cycles of pembrolizumab in the absence of disease progression or unacceptable toxicity. Beginning on cycle 1 day 1, participants also undergo standard of care intensity modulated radiation therapy (IMRT) once daily (QD) for 32 days over 6.5-8 weeks. Participants also undergo TURBT, cystoscopy, as well as imaging throughout the study.
  • Experimental: Dose Level 3: 1.25 mg/kg Enfortumab Vedotin
    Participants receive 1.25 mg/kg enfortumab vedotin intravenously (IV) over 30 minutes on days 1 and 8 of cycles 1-5 and pembrolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 5 cycles of enfortumab vedotin and up to 17 cycles of pembrolizumab in the absence of disease progression or unacceptable toxicity. Beginning on cycle 1 day 1, participants also undergo standard of care intensity modulated radiation therapy (IMRT) once daily (QD) for 32 days over 6.5-8 weeks. Participants also undergo TURBT, cystoscopy, as well as imaging throughout the study.
  • Experimental: Dose Expansion; Recommended Phase 2 Dose (RP2D)
    Participants receive RP2D of enfortumab vedotin intravenously (IV) over 30 minutes on days 1 and 8 of cycles 1-5 and pembrolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 5 cycles of enfortumab vedotin and up to 17 cycles of pembrolizumab in the absence of disease progression or unacceptable toxicity. Beginning on cycle 1 day 1, participants also undergo standard of care intensity modulated radiation therapy (IMRT) once daily (QD) for 32 days over 6.5-8 weeks. Participants also undergo TURBT, cystoscopy, as well as imaging throughout the study.

Primary Outcome Measure

Recommended phase II dose (RP2D) (Phase Ib) [ Time Frame: Up to 72 days ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
University of California, San FranciscoSan FranciscoCalifornia94143
UCSF Genitourinary Medical Oncology Recruitment
[email protected]
877-827-3222
[email protected]
Vadim Koshkin, MD (PRINCIPAL_INVESTIGATOR)

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By condition
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By specialty
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By research site
University of California, San Francisco· San Francisco, CA

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