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OncoMatch/Clinical Trials/NCT06470282

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

Is NCT06470282 recruiting? Yes, currently enrolling (May 2026). This Phase 1/2 trial studies multiple treatments including Pembrolizumab and Enfortumab Vedotin for bladder cancer.

Phase 1/2RecruitingUniversity of California, San FranciscoNCT06470282Data as of May 2026

Treatment: Enfortumab Vedotin · PembrolizumabThis 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.

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Extracted eligibility criteria

Cancer type

Urothelial Carcinoma

Disease stage

Excluded: Stage N2 OR HIGHER

Biopsy-confirmed muscle-invasive bladder cancer (cT2,T3,T4a). Presence of distant metastases on imaging (M1 disease) [excluded]. Presence of ≥ N2 disease on imaging (N1 disease allowed, but participants with N1 disease will be capped at 25% of patients treated at RP2D).

Performance status

ECOG 0–1(Restricted strenuous activity)

Prior therapy

No prior treatment (treatment-naive required)
Max 0 prior lines

Cannot have received: systemic immunotherapy

Exception: prior systemic therapy >12 months prior allowed; prior BCG and intravesical treatments allowed

Prior treatment with systemic immunotherapy or chemotherapy for urothelial cancer. (with the exception of prior systematic therapy treatment >12 months prior). Note: Prior bacillus calmette-guerin (BCG) and intravesical treatments are allowed

Cannot have received: systemic anti-cancer therapy including investigational agents

Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to cycle 1 day 1.

Cannot have received: radiotherapy

Has received prior radiotherapy within 2 weeks of cycle 1 day 1 or had radiation-related toxicities requiring corticosteroids.

Lab requirements

Blood counts

Absolute neutrophil count ≥ 1,500/mcL. Platelets >= 100,000/mcL. Hemoglobin >= 9.0 g/dL or ≥ 5.6 mmol/L. Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.

Kidney function

Creatinine clearance GFR >= 30 mL/min/1.73 m^2, calculated by Cockcroft-Gault or measured using 24-hour creatinine clearance.

Liver function

Total bilirubin <= 1.5 × ULN, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits. AST <= 2.5 × ULN. ALT <= 2.5 × ULN.

Absolute neutrophil count ≥ 1,500/mcL. Platelets >= 100,000/mcL. Hemoglobin >= 9.0 g/dL or ≥ 5.6 mmol/L. Total bilirubin <= 1.5 × ULN, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits. AST <= 2.5 × ULN. ALT <= 2.5 × ULN. Creatinine clearance GFR >= 30 mL/min/1.73 m^2.

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • University of California, San Francisco · San Francisco, California

Showing up to 5 US sites. See all sites on ClinicalTrials.gov →

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