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Efficacy of Enfortumab Vedotin plus Pembrolizumab in Adult Patients with Muscle‑Invasive Bladder Cancer Using a Bladder‑Sparing Response‑Adapted Approach

Fast replyRegistered drugNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

The study focuses on adults with urothelial bladder cancer that has spread to the muscle layer but can still be treated without removing the bladder. The treatment being tested combines two medicines given by IV infusion: enfortumab vedotin, which carries a toxin to cancer cells, and pembrolizumab, which helps the body’s immune system recognize and attack the tumor.

The purpose of the study is to determine whether this drug combination can allow the bladder to be preserved instead of undergoing surgery.

Participants receive the two drugs together at the start of the trial. After this initial phase, doctors evaluate how the tumor responded; if the cancer appears to have disappeared, some patients will receive additional radiation therapy (RT) while others will not, and all will continue to receive pembrolizumab over a longer period. The study follows participants for up to two years, tracking whether the bladder remains intact and monitoring safety, with extra testing such as circulating tumor DNA (ctDNA) to help predict outcomes.

The research process

The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Start induction therapy

    On day 1 you will receive an intravenous infusion of enfortumab vedotin at a dose of 125 mg per kilogram of body weight and an intravenous infusion of pembrolizumab at a dose of 400 mg. the two infusions are given on the same day.

    The study protocol defines how often these infusions are repeated during the induction period.

  2. Step 2

    Repeat induction cycles

    You will return for additional infusions of the same two drugs according to the schedule specified by the study, usually every few weeks, until the planned number of induction cycles is completed.

  3. Step 3

    Response evaluation

    After the induction cycles, doctors will examine your bladder using cystoscopy, imaging, or other tests to determine how the tumor has responded.

    The results will show whether a complete clinical response (ccr) has been achieved.

  4. Step 4

    Treatment decision based on response

    If a complete clinical response is observed, you may either skip further bladder‑directed treatment (no consolidation) or receive consolidative radiotherapy to the bladder.

    After radiotherapy, you may receive maintenance infusions of pembrolizumab as defined by the study protocol.

    If the tumor has not responded completely, the study may recommend cystectomy (surgical removal of the bladder) or other appropriate management.

  5. Step 5

    Follow‑up and monitoring

    Throughout the study you will have regular visits to monitor safety, tumor status, and bladder function.

    The study will continue to track outcomes for up to two years from the first day of treatment.

Who can join the trial?

10 criteria

  • Be at least 18 years old on the day you sign the consent form.
  • Provide a written consent form (or have a legal representative sign if you cannot).
  • Have bladder cancer that has been confirmed by a microscope (histologically confirmed) and is classified as cT2‑4aN0‑1M0, meaning the tumor is in the bladder wall but has not spread to distant organs.
  • Be looking for a bladder‑saving treatment instead of surgery, or be medically unable to have surgery.
  • If your tumor contains mixed cell types, it is allowed except if it is mostly (more than 90%) squamous cells, more than 50% adenocarcinoma, more than 50% sarcomatoid, more than 10% plasmacytoid, or any small‑cell component.
  • Provide a sample of your tumor tissue, either from an older (archival) sample or a new transurethral resection of bladder tumor (TURB); a preserved tissue block (FFPE) is preferred.
  • Have an ECOG performance status of 0 or 1, which means you are fully active or have only slight symptoms; this must be checked within 7 days before the first dose.
  • Have adequate function of major organs (such as liver, kidneys, and blood counts) as defined by the study, with testing done within 14 days before starting treatment.
  • If you are female, you must not be pregnant or breastfeeding, and you must either be unable to become pregnant or use a highly effective birth‑control method and have a negative pregnancy test within 72 hours before the first dose; you must also avoid breastfeeding for the required time after treatment.
  • If you are male, you must agree not to donate sperm and either avoid heterosexual intercourse or use contraception unless you have no sperm (azoospermic) for the required time after treatment.

Who cannot join the trial?

23 criteria

  • Previous pelvic irradiation (radiation treatment to the lower abdomen and pelvic area).
  • Having another cancer that is getting worse or needed active treatment in the past 3 years (skin basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ that was treated curatively are allowed; low‑risk prostate cancer under active surveillance is allowed).
  • Severe allergic reaction (grade 3 or higher) to pembrolizumab, EV, or any of their ingredients such as histidine, trehalose dihydrate, or polysorbate 20.
  • Active autoimmune disease that required whole‑body (systemic) treatment in the past 2 years (exceptions: hormone replacement like thyroxine or insulin, mild skin conditions like vitiligo or psoriasis, and gout are allowed; no active arthritis within 30 days).
  • History of non‑infectious lung inflammation (pneumonitis or interstitial lung disease) that required steroids or is still present.
  • Ongoing nerve damage (sensory or motor neuropathy) that is grade 2 or worse.
  • Active eye inflammation (keratitis) or corneal ulcers (unless superficial punctate keratitis is being treated adequately).
  • Uncontrolled diabetes, defined as HbA1c ≥ 8 % or HbA1c 7‑< 8 % with symptoms such as excessive urination (polyuria) or thirst (polydipsia) that are not explained.
  • Severe infections within the last 2 weeks, including hospitalization for infection, bloodstream infection (bacteremia), or serious pneumonia; any infection that needs systemic medication is excluded.
  • Active HIV infection, tuberculosis, or other active infections (certain HIV‑positive patients meeting strict criteria, controlled hepatitis B, and cured hepatitis C with undetectable virus are allowed).
  • Not fully recovered from major surgery or having ongoing surgical complications.
  • Cancer of the upper urinary tract (upper tract urothelial cancer).
  • Major pelvic surgery within 4 weeks before enrollment or expected need for such surgery during the study (except surgery for the bladder cancer being studied).
  • Any condition, treatment, lab abnormality, or situation that could confuse the study results or make participation unsafe, as judged by the doctor.
  • Known psychiatric illness or substance‑abuse disorder that would interfere with study participation.
  • Prior allogeneic tissue or solid‑organ transplant.
  • Extensive carcinoma in situ (CIS) of the bladder.
  • Blockage of both kidneys (bilateral hydronephrosis).
  • Previous intravenous systemic therapy for bladder cancer, such as chemotherapy, checkpoint inhibitors, or antibody‑drug conjugates.
  • Use of an investigational drug or device within 4 weeks before the study treatment.
  • Contra‑indication (medical reason not to use) to any component of the study treatment.
  • Receipt of a live or live‑attenuated vaccine within 30 days before the first dose (killed vaccines are allowed).
  • Diagnosis of immunodeficiency or use of chronic systemic steroids higher than 10 mg daily of prednisone‑equivalent, or any other immune‑suppressing therapy within 7 days before the first dose.
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Investigated drugs

  • Pembrolizumab

    is an immunotherapy medicine that helps your own immune system see and fight cancer cells. In this study it is given through an IV infusion and is used at the beginning of treatment to boost the body’s natural defenses against bladder cancer.

  • Enfortumab vedotin

    is a targeted therapy that combines an antibody with a chemotherapy drug. The antibody finds a protein on bladder cancer cells, and the attached chemotherapy is delivered directly to those cells, helping to kill them while sparing normal tissue. It is also given by IV infusion and is used together with pembrolizumab at the start of the trial to try to shrink the tumor before a response‑adapted plan is decided.

What is already known about the treatment

  • Pembrolizumab

    It is supplied as a 25 mg/mL concentrate that is mixed with fluid and given by intravenous infusion. Pembrolizumab is an approved cancer medicine that has been studied in many clinical trials. It is used mainly for bladder, lung and skin cancers by blocking the PD‑1 protein on immune cells, which helps the body’s own immune system attack the tumor. It belongs to the class of immune checkpoint inhibitor monoclonal antibodies.

  • Enfortumab vedotin

    It is provided as a 30 mg powder that is reconstituted and administered through an intravenous infusion. Enfortumab vedotin is an approved treatment for advanced bladder cancer and is being tested together with other drugs. The drug works by attaching to the Nectin‑4 protein on cancer cells and delivering a cell‑killing agent called MMAE directly into the tumor. It is classified as an antibody‑drug conjugate used as an antineoplastic agent.

Investigated diseases

Clinical stage T2‑4a N0‑1 muscle‑invasive urothelial carcinoma of the bladder - This cancer starts in the lining of the bladder and grows into the muscle layer. It may cause blood in the urine, urgency, or pain when urinating. As the tumor expands, it can involve nearby tissues and spread to lymph nodes. If it continues to grow, it can become more extensive within the bladder and beyond. The disease can advance from a localized tumor to one that involves deeper structures and regional nodes.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IITrial ID2026-525965-29-00Protocol codeM24FDLEstimated enrolment56 patientsSponsorHet Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

sourced from the EU Clinical Trials Register and site verification

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