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Enfortumab Vedotin and Pembrolizumab with Radiation for Bladder Cancer

This study is looking at a new way to treat muscle-invasive bladder cancer, which is cancer that has grown into the bladder wall. It combines two drugs, enfortumab vedotin and pembrolizumab, with radiation therapy. Researchers want to find the best dose of these treatments together and see how safe and effective they are. You may be able to join if you have muscle-invasive bladder cancer (stages II or IIIA) with urothelial histology, meaning the cancer cells look a certain way under a microscope. The study aims to see how many people have a complete response to the treatment, meaning the cancer is no longer detectable. The current status of this study is unclear, and it plans to enroll 47 participants.

Study design
This is an interventional study, meaning participants will receive specific treatments. It plans to enroll 47 participants.
What's involved
You would undergo a Transurethral Resection of Bladder Tumor (TURBT) and cystoscopy. You would also receive Enfortumab Vedotin and Pembrolizumab intravenously, and Intensity Modulated Radiation Therapy (IMRT).
Compensation
Not stated in the trial record.
Follow-up
The study will track treatment-emergent adverse events for up to 14 months. Other outcomes, like recurrence-free survival and overall survival, will be evaluated for up to 2 years.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT06470282

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

Recruiting
PHASE1Ages 18+InterventionalTreatment
University of California, San Francisco
~47 participants
Updated 2026-02-18 on ClinicalTrials.gov
What's tested:Enfortumab VedotinPembrolizumabIntensity Modulated Radiation Therapy (IMRT)Transurethral Resection of Bladder TumorCystoscopy (CS)Computed Tomography (CT)

At a glance

Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Recommended phase II dose (RP2D) (Phase Ib)
Measured over Up to 72 days
+3 more outcomes measured

Conditions

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

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Bladder Carcinoma

NCT06470282

Where you'd take part

This study runs at 1 site. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.

  • University of California, San Francisco

    San Francisco, Californiastudy coordinator listed

    Recruiting

Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.

Study leadership

  • Vadim Koshkin, MD · PRINCIPAL_INVESTIGATOR · University of California, San Francisco

Who to contact

UCSF Genitourinary Medical Oncology Recruitment
[email protected]
877-827-3222
Email the study team

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Eligibility criteria

Inclusion

Biopsy-confirmed muscle-invasive bladder cancer (cT2,T3,T4a). (Note: Tissue samples are required.) (Participants with cT3/T4a staged disease will be capped at 25% of patients treated at RP2D).
Urothelial histology present. Mixed histologies other than small cell/neuroendocrine are allowed as long as some urothelial histology is present. Neuroendocrine histology of any component and pure variant (non-urothelial) histology tumors will be excluded. (Patients with \< 50% urothelial histology will be capped at 25% of patients treated at RP2D).
Must be judged by the investigator to be ineligible for radical cystectomy or electing not to undergo radical cystectomy.
Must be eligible for and agree to receive bladder irradiation as determined by the treating investigator.
Must have a TURBT within 8 weeks of combination treatment start with viable tumor content. If no viable tumor content is present on TURBT, the patient will be replaced in the study.
Patients who have autoimmune disease will be evaluated on a case-by-case basis and can only enroll so long as participants are not on active immunosuppression with a corticoid steroid allowance exceeding 10mg of prednisone or equivalent per day.
Age \>= 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status \<= 1.
Absolute neutrophil count ≥ 1,500/microliter (mcL).
Platelets \>= 100,000/mcL.
Hemoglobin \>= 9.0 g/dL or ≥ 5.6 mmol/L.
Total bilirubin \<= 1.5 × upper limit of normal, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits.
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT)) \<= 2.5 X institutional upper limit of normal.
Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (SGPT)) \<= 2.5 X institutional upper limit of normal.
Creatinine clearance glomerular filtration rate (GFR) \>= 30 mL/min/1.73 m\^2, calculated by Cockcroft-Gault or measured using 24-hour creatinine clearance.
International normalized ratio (INR) OR prothrombin time (PT) \<= 1.5 × upper limit of normal (ULN).
Activated partial thromboplastin time (aPTT) \<= 1.5 × ULN.
Ability to understand and the willingness to sign a written informed consent document.
Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
Participants who are hepatitis B virus surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) anti-viral therapy for at least 4-weeks, and have undetectable HBV viral load prior to randomization. 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 a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.
Women of child-bearing potential and men with sexual partners of childbearing potential must agree to use adequate contraception for the duration of study participation. Enfortumab vedotin (EV) may cause fetal harm. Women of child-bearing potential must use contraception during treatment with EV and for 120 days after the last dose. Men with female partners who are women of child-bearing potential must use contraception during treatment with EV and for 120 days after the last dose. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Acceptable methods include barrier method, hormonal method, as well as intrauterine devices
Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 8 weeks after last administration of study treatment.

Exclusion

Presence of distant metastases on imaging (M1 disease).
Presence of ≥ N2 disease on imaging (N1 disease allowed, but participants with N1 disease will be capped at 25% of patients treated at RP2D).
Presence of small cell / neuroendocrine histology in tumor sample (any content).
Absence of urothelial histology in TURBT tumor sample (pure variant histology).
Presence of untreated upper tract urothelial cancer.
Presence of severe hydronephrosis precluding therapy in the judgement of the treating physician.
Presence of extensive carcinoma in situ (CIS) is exclusionary; moderate CIS that could still benefit from radiation treatment in the judgement of treating physician is allowed.
Baseline neuropathy grade 2 (G2) or greater.
Baseline uncontrolled diabetes mellitus.Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥ 8% or HbA1c 7 to \< 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
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
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to cycle 1 day 1.
Has received prior radiotherapy within 2 weeks of cycle 1 day 1 or had radiation-related toxicities requiring corticosteroids.
Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention.
Major surgery within 2 weeks prior to first dose of EV.
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.
HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
Has known active CNS metastases and/or carcinomatous meningitis.
History of another significant life-limiting malignancy requiring systematic treatment within 2 years prior to the first dose of study drugs, or any evidence of residual disease from a previously diagnosed malignancy.
Hypersensitivity to pembrolizumab or enfortumab vedotin, or any of their excipients.
Prior allogeneic stem cell or solid organ transplant.
Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
Has an active infection requiring systemic therapy.
Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
History of Hepatitis B with detectable HBV viral load (participants who are HBsAg positive are eligible if they have received HBV anti-viral therapy for at least 4 weeks, and/or have undetectable HBV viral load prior to randomization) or known active hepatitis C virus (defined as detectable HCV RNA .\[qualitative\]) infection.
Pregnant and breast feeding participants are excluded from this study because targeted chemotherapy and radiation have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with EV+pembrolizumab, breastfeeding should be discontinued if the mother is treated with these investigational products.

What this trial measures

  • Recommended phase II dose (RP2D) (Phase Ib)Up to 72 days

    The RP2D is the last dose cohort at which no more than one instance of a dose limiting toxicity (DLT) is observed among 6 participants treated. If the maximum tolerated dose (MTD) cannot be determined due to lack of DLT during the DLT window, the maximum dose level of enfortumab vedotin administered during the study will be declared the RP2D. For the purposes of this study, the RP2D is the MTD.

  • Proportion of participants reporting dose limiting toxicities (DLTs) (Phase Ib)Up to 72 days

    The DLT evaluation period will be within the first three cycles (e.g., 56 days or eight weeks, and not to exceed 72 days) of treatment start with enfortumab-vedotin, pembrolizumab, and standard of care fractionation radiation therapy. Participants who receive \> 75% of intended enfortumab vedotin, pembrolizumab, and standard of care radiation doses will be considered DLT evaluable (DE).

  • Frequency of treatment-emergent adverse eventsUp to 14 months

    The frequency of adverse events by highest grade and overall attribution to study drugs, according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  • Percentage of participants with Clinical complete response (cCR) (Phase II)Up to 6 months

    The rate of clinical complete response to treatment (cCR) will be measured as the percentage of participants with cCR based on cystoscopy and TURBT done at 6 months from treatment start. cCR is defined as no visual tumor AND no histological presence of tumor (i.e., ypT0).