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Urothelial Bladder CarcinomaPhase 2NCT06133517

PeRioperative Immunotherapy Combined With Sacituzumab Govitecan in Muscle Invasive blAdder Cancer

A Phase 2 study testing Sacituzumab govitecan, Zimberelimab and Domvanalimab in people with Urothelial Bladder Carcinoma, run by Fundación para el Progreso de la Oncología en Cantabria at 6 sites in Spain.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The main objective of this trial is to evaluate the efficacy of the combo Sacituzumab govitecan (SG) + Zimberelimab (AB 122) (ZIM) + Domvanalimab (AB 154) (DOM), measured as pathologic complete response (pCR) rates, in the perioperative setting in patients with Muscle Invasive Bladder Cancer (MIBC) who are either… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urothelial Bladder Carcinoma
What is being tested?
Sacituzumab govitecan, Zimberelimab and Domvanalimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
6 sitesSpain
Study dates
20 Jan 2025to Dec 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Willing and able to provide written informed consent.
  • Ability to comply with the study procedures and requirements and restrictions in this protocol.
  • Age ≥ 18 years.
  • Muscle invasive urothelial carcinoma stage cT2-T4cN0-1cM0. Patients with mixed histologies are required to have a dominant (i.e. 50% at least) urothelial carcinoma pattern.
  • Fit and planned for cystectomy (according to local guidelines).
  • Refusal of neoadjuvant cisplatin-based chemotherapy or patients in whom neoadjuvant cisplatin-based therapy is not appropriate. (This will be determined by the investigator and not solely based in Galsky Criteria).
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  • Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for testing at the study sponsor site. Patients with fewer than 15 unstained slides available at baseline (but no fewer than 10) may be eligible following discussion with the PI of the study.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
  • Adequate hematologic and end-organ function tests defined by the following:
  • White Blood Cell (WBC) ≥ 2.0x109/L,
  • Neutrophils ≥1.5x109/L,
  • Platelets ≥100 x109/L,
  • Hemoglobin ≥ 10 g/dL,
  • Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation
  • Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal(ULN),
  • Alanine aminotransferase (ALT) ≤2.5 x ULN,
  • Bilirubin ≤1.5 X ULN.
  • Adequate coagulation (Prothrombin Time [PT]) or International Normalized Ratio [INR] and Activated Partial Thromboplastin Time [aPTT]) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • Negative pregnancy test within 3 days of Day 1 Cycle 1 for female patients of childbearing potential.
  • Male patients and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.

Who cannot join

  • Concurrent enrollment in another interventional clinical trial, unless in a follow-up period or it is an observational study.
  • Having received previous anticancer therapy including:
  • Any investigational anticancer therapy received within 28 days or 5 half-lives (whichever is longer) of first dose of study treatment.
  • Any previous intravenous chemotherapy specific for bladder cancer.
  • Previous systemic treatment with topoisomerase 1 inhibitors.
  • Prior Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) or Programmed death-1(PD-1)/ programmed death-ligand 1(PD-L)1-targeting immunotherapy.
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  • Previous treatment with high dose chemotherapy and bone marrow transplant
  • Previous radiotherapy specific for bladder cancer
  • Underlying medical conditions that might make the administration of study drugs hazardous or that might obscure the interpretation of adverse events including:
  • 3.1 Known or suspected autoimmune disease. Patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus or autoimmune vasculitis (e.g., Wegener's granulomatosis) are excluded from this study; Patients with other autoimmune disorders such as a history of Hashimoto's thyroiditis [only requiring hormone replacement], type I diabetes, psoriasis [not requiring systemic treatment], or conditions not expected to recur in the absence of an external trigger are allowed to participate.
  • 3.2 History of primary immunodeficiency.
  • 3.3 A positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA), active tuberculosis, or other active infection requiring therapy at the time of inclusion.
  • HIV positive patients are allowed as far as they have the disease controlled according to their treating physicians based on lymphocyte counts and viral load.
  • 3.4 Medical conditions requiring the use of immunosuppressive medications, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication) will be allowed.
  • Patient receiving treatment with inhibitors or inducers of UGT1A1 at the time of enrollment.
  • Patient receiving treatment with high dose systemic corticosteroids (>10 mg of prednisone or its equivalent) within 2 weeks of C1D1.
  • Patients who have received a vaccination within 30 days prior to inclusion (examples include, but are not limited to, intranasal influenza vaccines, typhoid [oral] vaccines, and Bacillus Calmette-Guerin [BCG]). Patients are allowed to receive the COVID-19 vaccine to reduce the risk and complications of COVID-19 infection. The study visits should continue as planned if vaccination occurs while the patient is on the study.
  • Malignancy, other than urothelial cancer, in the previous 2 years. Patients with low-risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 6, and Prostatic specific antigen (PSA) ≤ 10 ng/mL) appropriately treated or that are treatment-naive and undergoing active surveillance are eligible. Also, noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin, or ductal carcinoma in situ of the breast, that have undergone potentially curative therapy are not excluded.
  • Major surgical procedure within 4 weeks prior to enrollment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis or treatment of its urothelial cancer.
  • Severe infection within 4 weeks prior to enrollment in the study including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
  • Met any of the following criteria for cardiac disease:
  • Myocardial infarction or unstable angina pectoris within 6 months of enrollment.
  • History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication).
  • History of QT interval prolongation.
  • Patient currently on dialysis.
  • Gastrointestinal perforation within 6 months of enrollment.
  • Patients who have organ allografts.
  • Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
  • Known allergy or hypersensitivity to study drugs formulations.
  • Patients who have invasive catheters that under the investigator criteria might put the patient at risk of developing severe complications due to neutropenia development.
  • Females who are pregnant, lactating, or intend to become pregnant during their participation in the study.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Spain6 sites

  • Hospital Duran i Reynals (ICO L´Hospitalet)

    L'Hospitalet de Llobregat, Barcelona

  • Hospital Clínico San Carlos

    Madrid, Madrid

  • Hospital Universitario de Navarra

    Pamplona, Navarre

  • Hospital Universitario Marqués de Valdecilla

    Santander, Cantabria

  • Hospital Virgen de la Salud

    Toledo, Toledo

  • Hospital Clinico Universitario de Valladolid

    Valladolid, Valladolid

Other trials in Spain

About this study

Official title: An Open Label, Single-arm, Phase 2 Study of Perioperative Sacituzumab Govitecan in Combination With Zimberelimab and Domvanalimab for Patients With Muscle Invasive Bladder Cancer Ineligible for Cisplatin-based Chemotherapy

The main objective of this trial is to evaluate the efficacy of the combo Sacituzumab govitecan (SG) + Zimberelimab (AB 122) (ZIM) + Domvanalimab (AB 154) (DOM), measured as pathologic complete response (pCR) rates, in the perioperative setting in patients with Muscle Invasive Bladder Cancer (MIBC) who are either unfit for platinum-based chemotherapy or unwilling to receive that therapy.

Read the detailed description

This is an open label, multicenter, single arm, phase II clinical trial, which aims to evaluate the effects of perioperative treatment with sacituzumab govitecan, zimberelimab and domvanalimab in patients with confirmed histological diagnosis of urothelial bladder carcinoma pT2-T4a cN0-1 cM0 non-eligible or who refuse to receive cisplatin-based neoadjuvant chemotherapy.

Patients who are eligible to participate in the study will receive 3 cycles of sacituzumab govitecan, zimberelimab and domvanalimab every 3 weeks prior to cystectomy, unless there are signs of unacceptable toxicity, progressive disease or the patient requests withdrawal from the study. Patients who do not achieve a pCR or that achieving a pCR still have positive ctDNA will also complete an adjuvant phase of the study consisting of 12 additional cycles of zimberelimab and domvanalimab.

To progressively test the safety of the proposed combination, this study has been developed in two stages with the aim of preserving patient's safety as a priority. This study includes a preliminary assessment about the safety of the combinations. Thus, there will be a safety run-in period in which 8 patients will receive the SG+ZIM combination to confirm the tolerability of this doublet in patients with MIBC.

Once the safety of this doublet has been confirmed by an external safety committee then the study will proceed to an additional safety-run in cohort with the triplet.

Being tested
Sacituzumab govitecan, Zimberelimab, Domvanalimab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sacituzumab govitecanDrug

    Also called Trodelvy

    Sacituzumab govitecan is administered at 10 mg/kg as an intravenous (IV) infusion on Days 1 and 8 of a 21-day cycle.

  • ZimberelimabDrug

    ZIM is administered at 360 mg every 3 weeks as an intravenous (IV) infusion on Day 1 of a 21-day cycle.

  • DomvanalimabDrug

    DOM is administered at 1200 mg every 3 weeks as an intravenous (IV) infusion on Day 1 of a 21-day cycle.

Study groups in NCT06133517
Study groupRoleWhat they receive
Single ArmExperimentalPatients who are eligible to participate in the study will receive 3 cycles of sacituzumab govitecan, zimberelimab and domvanalimab every 3 weeks prior to cystectomy, unless there are signs of unacceptable toxicity, progressive disease, or the patient requests withdrawal from the study. Patients who do not achieve a pCR or that achieving a pCR still have positive ctDNA will also complete an adjuvant phase of the study consisting of 12 additional cycles of zimberelimab and domvanalimab after cystectomy.
Receives: Drug: Sacituzumab govitecan; Drug: Zimberelimab; Drug: Domvanalimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To evaluate the efficacy measured as pathologic complete response rates of the combo SG+ZIM+DOM in the perioperative setting in patients with MIBC who are either unfit for platinum-based chemotherapy or unwilling to receive that therapy.

    Efficacy of the combination of sacituzumab govitecan, zimberelimab and domvanalimab measured as pathologic complete response (pCR) rates.

    pCR is defined as absence of residual viable tumor (ypT0) in the radical cystectomy specimen and in the resected lymph nodes (ypN0) (post-treatment).

    Measured: 42 months

Secondary outcomes (6)

  1. To evaluate the downstaging rate induced by the combo

    Downstaging is defined as any non-muscle invasive residual disease after treatment in the cystectomy specimen (i.e ypTis, ypTa,ypT1).

    Measured: 42 months

  2. To measure overall survival (OS) and disease-free survival (DFS) in the study population

    OS is defined as the time from informed consent signature to death from any cause.

    Measured: 42 months

  3. To evaluate the safety of the combo

    Safety and tolerability of the combination of sacituzumab govitecan, zimberelimab and domvanalimab measured as the incidence, nature and severity of adverse events (AEs).

    Measured: 42 months

  4. To identify predictive biomarkers associated with response to SG + ZIM + DOM.

    Cancer associated fibroblast (CAFs) as predictors of response. Immune sub-populations as predictors of response

    Measured: 42 months

  5. To gain knowledge about the role of ctDNA in the perioperative setting

    This parameter will be measured by ctDNA clearance, defined as the proportion of patients who are ctDNA positive at baseline and ctDNA negative after concluding the neoadjuvant component of the treatment, at the time of concluding neoadjuvant treatment and at the time post cystectomy.

    Measured: 42 months

  6. To explore the role of adjuvant ZIM+DOM in selected patients after definitive surgical treatment

    DFS event is defined as any of the following: development of distant metastasis of urothelial carcinoma or presence of pelvic recurrence of urothelial carcinoma (including soft tissue and regional lymph nodes) or death from any cause.

    OS is defined as the time from informed consent signature to death from any cause.

    Measured: 42 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Nov 2023
  2. Study start20 Jan 2025
  3. Primary completionJan 2030 (estimated)
  4. Study completionDec 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06133517
Sponsor's protocol ID
PRISMA-1
Other IDs
2023-504420-26-00, 2023
Status last verified
Oct 2026
First submitted
10 Nov 2023
Last updated
7 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sacituzumab govitecan, Zimberelimab and Domvanalimab in people with Urothelial Bladder Carcinoma, run by Fundación para el Progreso de la Oncología en Cantabria at 6 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 7 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To evaluate the efficacy measured as pathologic complete response rates of the combo SG+ZIM+DOM in the perioperative setting in patients with MIBC who are either unfit for platinum-based chemotherapy or unwilling to receive that therapy. (time frame: 42 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06133517.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2026; AzTrials last refreshed its copy on 8 Nov 2026.

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