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Study of ivonescimab plus enfortumab vedotin versus pembrolizumab plus enfortumab vedotin in previously untreated locally advanced or metastatic urothelial carcinoma

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What is this study about?

The trial focuses on Locally Advanced or Metastatic Urothelial Carcinoma, a form of bladder cancer that has spread beyond the bladder. Two treatment combinations are being compared: one uses the experimental antibody ivonescimab together with the antibody‑drug conjugate enfortumab vedotin, and the other uses the approved immune therapy pembrolizumab together with enfortumab vedotin.

The purpose of the study is to compare how well the experimental combination works against the standard combination in terms of safety and how long patients live without the disease getting worse.

Participants receive an intravenous infusion (medicine given through a vein) of the assigned drugs every three weeks for up to one year, with regular clinic visits for physical checks, blood tests, and imaging scans to see how the cancer responds. After treatment stops, patients are followed for several months to monitor long‑term outcomes.

1 initial treatment infusion

after joining the study you will receive the first intravenous infusion of the medication combination assigned to you. the combination may be ivonescimab at a dose of 20 mg per kilogram of body weight together with enfortumab vedotin at a dose of 1.5 mg per kilogram, or it may be pembrolizumab at a dose of 1.25 mg per kilogram together with enfortumab vedotin at a dose of 1.5 mg per kilogram. the drugs are given through a vein (intravenous infusion).

the infusion is performed in a clinical setting where health professionals monitor you during the administration to ensure safety.

2 subsequent treatment infusions

following the initial infusion you will continue to receive the same combination of medicines by intravenous infusion at regular intervals according to the study schedule. each infusion contains the same doses as the first infusion: 20 mg/kg of ivonescimab plus 1.5 mg/kg of enfortumab vedotin, or 1.25 mg/kg of pembrolizumab plus 1.5 mg/kg of enfortumab vedotin.

the frequency of these infusions (for example, every two weeks) is determined by the study protocol and will be followed throughout the trial period.

3 completion of treatment phase

treatment continues with each scheduled infusion until the end of the study period, until the investigators decide to stop treatment because of disease progression, side effects, or other clinical reasons defined in the protocol.

after the final infusion you will have a concluding visit where study assessments are performed to gather the last set of data.

Who Can Join the Study?

  • ECOG performance status score of 0 or 1, meaning you are fully active or able to carry out light work.
  • Expected life expectancy of at least 6 months.
  • Diagnosis confirmed by a tissue test (histologically documented) of an unresectable (cannot be removed by surgery) locally advanced or metastatic urothelial cancer in the bladder, kidney area, ureter, or urethra, with at least half of the tumor made up of urothelial cells; mixed‑type tumors are allowed if the urothelial part is 50% or more.
  • No previous whole‑body (systemic) treatment for this cancer, except that earlier (neoadjuvant or adjuvant) therapy is allowed only if the cancer came back more than 12 months after the last dose.
  • At least one tumor that can be measured on scans outside the brain, using standard criteria (RECIST v1.1); lesions that were previously treated with radiation can be measured if they have shown growth since that treatment.
  • You must have a way to determine your PD‑L1 status before randomization, either by having an existing test result or by providing a tissue sample (stored as formalin‑fixed, paraffin‑embedded (FFPE) tissue) for a new test.

Who Cannot Join the Study?

  • If your cancer can be cut out by surgery or treated locally with the goal of curing it (resectable or suitable for local therapy with curative intent), you cannot take part in the study.
  • If any part of your tumor looks like small cell or neuroendocrine cancer, you are not eligible. You also cannot join if more than half of the tumor looks like squamous, glandular, micropapillary or sarcomatoid types. (These terms describe different shapes and patterns of cancer cells.)
  • If you currently have nerve problems that cause loss of feeling or muscle weakness that are moderate or worse (sensory or motor neuropathy Grade 2 or higher), you cannot join. (Sensory neuropathy = nerve damage affecting feeling; motor neuropathy = nerve damage affecting movement; Grade 2 = moderate severity.)
  • If you have an active eye inflammation (keratitis) or an open sore on the eye surface (corneal ulcerations), you cannot join. A mild form called superficial punctate keratitis is allowed only if it is being treated well.
  • If imaging scans show a high risk of bleeding because the tumor is growing into or wrapping around large blood vessels (radiographic findings of major blood vessels involvement or encasement), you cannot join.
  • If you have had serious heart or blood‑vessel problems that required a hospital stay in the past year, you cannot join. This includes unstable chest pain (unstable angina), a heart attack (myocardial infarction), serious heart failure (congestive heart failure worse than NYHA class II), or dangerous vessel disease such as a large artery bulge that could burst (aortic aneurysm) or a rare brain vessel condition (Moyamoya disease). You also cannot join if you have other heart issues that could affect safety, such as badly uncontrolled irregular heartbeats (arrhythmias) or reduced blood flow to the heart (myocardial ischemia).

Where you can join this trial?

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Site Name City Country Status
Hksubmvj Vkne dywyrasg Barcelona Spain
Vsjbzp dks Rizyq Ucbfbejtqy Hylfxedq Sevilla Spain
Hnanighd Uknazmeivobfp Qmruklltirj Mojson Pozuelo De Alarcon Spain
Utnmelxbchfq Ds Sidksanw Di Cayaxzgxwi Santiago De Compostela Spain
Htlpduxw Cllkosj Stv Crdfzb Madrid Spain
Hunqfoip Uxuzlvnemixub Llotv Akebjmd Lugo Spain
Szzaw Sfvf Jsyy Do Rikd Reus Spain
Hczqfdhy Ubnsoipriozvs Peeapk Du Hijxhe Dk Mgmzmtgadyf Majadahonda Spain
Hnoppojd Uhyfjcvgmxzrm 1u Da Omqqxjv Madrid Spain
Hucphaty Uhjjczsaoomiq Mmsjqgz Dk Vxtulcfmsw Santander Spain
Hjneyilv Ustilmoizwqep Dp Bngvlnx Badajoz Spain
Fcngoshwg Pduw Lb Izutxhkarekvw Bibnjwkik Dth Hfhxmmpq Uvuwvhtqjjjam La Peb Madrid Spain
Ideeupcvc Oxickvxgsk Dlg Rcjzet Swty Barcelona Spain

Want to learn more about this study or check if you can participate? Contact us.

Trial status

Country Status Recruitment Start
Spain Spain
Not yet recruiting
01.11.2026

Trial locations

Investigated Drugs:

Ivonescimab is an experimental antibody being tested for the first time in this study. It is designed to attach to a specific protein on cancer cells and help the immune system recognize and attack those cells. In the trial, it is given together with another drug to see if the combination works better than the current standard treatment.

Pembrolizumab is an approved immunotherapy that helps the body’s immune system see and fight cancer. It works by blocking a checkpoint that normally tells immune cells to stay calm, allowing them to become more active against tumor cells. In this study, it is used together with another drug as the standard‑of‑care treatment for comparison.

Enfortumab vedotin is a targeted cancer medicine that combines an antibody with a chemotherapy drug. The antibody part finds a protein that is common on bladder cancer cells, and the attached chemotherapy is then delivered directly to those cells, helping to kill them while sparing most normal cells. It is used in both treatment groups in the trial.

Investigated Diseases:

Locally advanced or metastatic urothelial carcinoma – Urothelial carcinoma is a cancer that begins in the lining of the urinary tract, most often the bladder. When it is locally advanced, the tumor has grown beyond the inner layer into surrounding tissue. Metastatic disease indicates that cancer cells have spread to distant sites such as lymph nodes, lungs, or bones. The cancer may cause urinary symptoms and can increase in size over time. Cancer cells keep dividing and may form new tumors in other parts of the body. Progression is tracked by imaging that shows changes in tumor size or spread.

Trial ID:
2026-525831-17-00
Protocol code:
SMT112-3008
NCT ID:
NCT06491472
Trial Phase:
Therapeutic use (Phase IV)

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