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Urothelial Bladder CancerPhase 2FIDELIONCT07663747

Enfortumab Vedotin + Pembrolizumab Induction to Spare the Bladder in MIBC

A Phase 2 study testing Enfortumab Vedotin, Pembrolizumab and Radiation in people with Urothelial Bladder Cancer, run by The Netherlands Cancer Institute at 3 sites in Netherlands.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

This is a Phase 2 clinical intervention trial to assess efficacy of induction EVP to spare the bladder in stage T2-4aN0-1 urothelial bladder cancer (UBC), using a response-adapted approach Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urothelial Bladder Cancer
What is being tested?
Enfortumab Vedotin, Pembrolizumab and Radiation
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
3 sitesNetherlands
Study dates
1 Sep 2026to 1 Apr 2032
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

  • Participants who are at least 18 years of age on the day of signing informed consent.
  • The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
  • Patients with histologically confirmed cT2-4aN0-1M0 urothelial bladder cancer, seeking an alternative to radical cystectomy and/or patients who are medically unfit for surgery.
  • Variant histology allowed, exceptions:
  • no pure (>90%) squamous
  • no >50% adenocarcinoma
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  • no >50% sarcomatoid component
  • no >10% plasmacytoid component
  • no small cell component
  • Archival tumor tissue sample or newly obtained TURB of the bladder tumor is available. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
  • Have adequate organ function as defined in Table 3 below. Specimens must be collected within 14 days prior to the start of study intervention.
  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
  • Not of childbearing potential (see section 9.2.1) OR
  • Of childbearing potential and:
  • Uses a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) during the intervention period and for at least 120 days (pembrolizumab) or 180 days (EV) after the last dose of study intervention and agrees not to donate ova to others or freeze/store for her own use for the purpose of reproduction before start of study treatment. More details on contraceptive guidance can be found in section 9.2.1. The investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) in relationship to the first dose of study intervention.
  • Has a negative urine or serum pregnancy test within 72 hours before the first dose of study intervention. Female subjects with false positive results and documented verification of negative pregnancy status may be eligible in consultation with the sponsor.
  • Abstains from breastfeeding during the study intervention period and for at least 120 days after study intervention (for pembrolizumab) or 180 days (EV) after the last dose of study intervention.
  • A male participant agrees to the following during the intervention period and for at least 180 days after the last dose of EV:
  • Refrains from donating sperm plus either:
  • Abstains from heterosexual intercourse as their preferred and usual lifestyle and agrees to remain abstinent
  • Uses contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause)

Who cannot join

  • Previous pelvic irradiation
  • Upper tract urothelial cancer
  • Extensive carcinoma in situ (CIS) of the bladder
  • Bilateral hydronephrosis
  • Previous intravenous systemic therapy for bladder cancer, including chemotherapy, checkpoint inhibition or antibody-drug conjugate.
  • Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
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  • Contra-indication to one of the study treatment components
  • Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
  • 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.
  • Known additional malignancy that is progressing or has required active treatment within the past 3 years.
  • Exceptions: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ that have undergone potentially curative therapy are not excluded. Patients with low-risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 6, and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible.
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab, EV and/or any of its excipients in drug formulations (including histidine, trehalose dihydrate, and polysorbate 20).
  • Has active autoimmune disease that has required systemic treatment in the past 2 years. Exceptions that can still be included:
  • Endocrine disease with replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid)
  • Patients with vitiligo, psoriasis or other mild skin disease
  • Gout is not considered an auto-immune disease. Patients should not have had an episode of active arthritis within 30 days of start of therapy.
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Ongoing sensory or motor neuropathy Grade 2 or higher.
  • Active keratitis or corneal ulcerations. Participants with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator.
  • A history of uncontrolled diabetes. Uncontrolled diabetes is defined as HbA1c ≥8% or HbA1c 7% to < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
  • Severe infections within 2 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia. Active infection requiring systemic therapy is excluded as well.
  • Known active Human Immunodeficiency Virus infection, or tuberculosis, or other active infection:
  • HIV-positive patients are eligible if the following applies:
  • Receives antiretroviral therapy (ART), without changes in drugs or dose modification, for at least 4 weeks prior to treatment and continued while enrolled on study.
  • CD4+ T-cell count ≥350 cells/mm3 at the time of screening
  • Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening
  • No AIDS defining opportunistic infection within the past 12 months, or a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
  • In patients with a known history of hepatitis B infection, Hepatitis B surface antigen should be negative at time of screening. Patients having chronic hepatitis B are not eligible.
  • Participants with a history of HCV infection are eligible if HCV viral load is undetectable at screening. Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.
  • Has not adequately recovered from major surgery or has ongoing surgical complications.
  • Major pelvic surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for the disease under study.
  • 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 ability to cooperate with the requirements of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Has had an allogenic tissue/solid organ transplant.

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Michiel S van der Heijden, MD,PhD contact

+31205122671

ms.vd.heijden@nki.nl

Okan Ghedri, MD contact

+31205122671

o.ghedri@nki.nl

Netherlands3 sites

  • Antoni van Leeuwenhoek ziekenhuis

    Amsterdam

    Michiel S van der Heijden, MD,PhD, +31205122671, fidelio@nki.nl

  • Leiden University Medical Center Leiden (LUMC)

    Leiden

    Tom van der Hulle, MD,PhD, +31 071 526 91 11

  • University Medical Center Utrecht(UMCU)

    Utrecht

    Britt Suelmann, MD,PhD, +31 088 75 555 55

Other trials in Netherlands

About this study

Official title: A Phase 2 Study to Assess Efficacy of Induction Enfortumab Vedotin Plus Pembrolizumab Using a Response-adapted Approach to Spare the Bladder: FIDELIO

This is a Phase 2 clinical intervention trial to assess efficacy of induction EVP to spare the bladder in stage T2-4aN0-1 urothelial bladder cancer (UBC), using a response-adapted approach

Read the detailed description

Fifty-six adult patients with cT2-4aN0-1 urothelial bladder cancer, who are amenable for a bladder-sparing approach, will be included

All patients receive induction (4x) Enfortumab vedotin (d1,8; 1.25mg/kg) and Pembrolizumab (d1; 200mg).

Patients having a clinical complete response (cCR) are randomized 1:1 to receive:

  1. No bladder consolidation therapy, pembrolizumab 400 mg q6 weeks maintenance (total 1 year from start of therapy), or
  2. Consolidative radiotherapy followed by pembrolizumab 400 mg q6 weeks maintenance (total 1 year from start of therapy).

Patients having residual disease:

  1. may still receive bladder-sparing treatment using chemoradio-therapy (by local protocol; Mitomycin C/fluoropyrimidines in the Netherlands) if the following criteria are met:
  • No disease outside the bladder (e.g. involvement of ureter, prostatic urethra or (suspected) lymph node metastases)
  • No bilateral hydronephrosis
  • No multifocal CIS
  • Adequate bladder function: post-micturition residual volume of < 200 cc, IPSS score < 15 points; revised urinary incontinence scale < 8 points; no daily or continuous catheter use. Bladder sparing treatment is followed by pembrolizumab 400 mg q6 weeks maintenance (total 1 year from start of therapy).
  1. In addition, patients having residual disease without the option of bladder sparing treatment, will undergo radical cystectomy followed by pembrolizumab 400 mg q6 weeks maintenance (total 1 year from start of therapy).

The induction phase will be approximately 14 weeks up until the point of consolidation/observation, which is followed by pembrolizumab maintenance for a maximum of six cycles. Protocol-specified follow-up (excluding survival follow-up) will continue until 36 months after consolidation. Survival follow-up will continue as long as the study remains open.

Being tested
Enfortumab Vedotin, Pembrolizumab, Radiation, Chemoradiation, Cystectomy

What participants receive

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

  • Enfortumab VedotinDrug

    Also called Padcev

    Induction: 4 cycles (d1,8; 1.25 mg/kg)

  • PembrolizumabDrug

    Also called Keytruda

    Induction: 4 cycles 200mg and after cCR 400 mg q6 weeks. Total 1 year from start of therapy

  • RadiationRadiation

    The preference will be a four-week schedule, in which 55 Gy radiotherapy will be administered using intensity modulated radiation therapy (IMRT)

  • ChemoradiationOther

    by local protocol; by local protocol; Mitomycin C/fluoropyrimidines in the Netherlands)

    • No disease outside the bladder (e.g. involvement of ureter, prostatic urethra or (suspected) lymph node metastases)
    • No bilateral hydronephrosis
    • No multifocal CIS
    • Adequate bladder function: Post-micturition residual volume of < 200 cc, International Prostate Symptom Score (IPSS) < 15 points; revised urinary incontinence scale < 8 points; no daily or continuous catheter use.

  • CystectomyProcedure or surgery

    Surgical removal of the bladder

Study groups in NCT07663747
Study groupRoleWhat they receive
After induction therapy and cCR: maintenance pembrolizumab onlyExperimentalPatients receive four 3-weekly cycles of induction Enfortumab Vedotin on days 1, 8 and Pembrolizumab day 1. If, after tumor assessment, the response is deemed a cCR, patients can be randomized to this group. This arm will receive Pembrolizumab maintenance: 400 mg q6weeks.
Receives: Drug: Enfortumab Vedotin; Drug: Pembrolizumab
After induction therapy and cCR: consolidative radiotherapy, followed by maintenance pembrolizumab.ExperimentalPatients receive four 3-weekly cycles of induction Enfortumab Vedotin on days 1, 8 and Pembrolizumab day 1. If, after tumor assessment, the response is deemed a cCR, patients can be randomized to this group. This arm will receive consolidative radiotherapy followed by Pembrolizumab maintenance: 400 mg q6weeks.
Receives: Drug: Enfortumab Vedotin; Drug: Pembrolizumab; Radiation: Radiation
By residual disease may still receive bladder-sparing treatmentOtherPatients receive four 3-weekly cycles of induction Enfortumab Vedotin on days 1, 8 and Pembrolizumab day 1. If, after tumor assessment, the response is deemed a non-cCR, patients can be placed in this group. In this arm, patients may still receive bladder-sparing treatment using chemoradiotherapy (by local protocol; Mitomycin C/fluoropyrimidines in the Netherlands), followed by Pembrolizumab maintenance: 400 mg q6weeks.
Receives: Drug: Enfortumab Vedotin; Drug: Pembrolizumab; Other: Chemoradiation
By residual disease cannot receive bladder-sparing treatmentOtherPatients receive four 3-weekly cycles of induction Enfortumab Vedotin on days 1, 8 and Pembrolizumab day 1. If, after tumor assessment, the response is deemed a non-cCR, patients can be placed in this group. In this arm, patients will undergo a radical cystectomy, followed by Pembrolizumab maintenance: 400 mg q6weeks.
Receives: Drug: Enfortumab Vedotin; Drug: Pembrolizumab; Procedure: Cystectomy

What is being measured

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

  1. Estimated 2-year bladder-intact event-free survival (BI-EFS) for the intention-to-treat population, measured from day 1 of treatment until the moment of analysis

    Bladder-intact event-free survival (BI-EFS). The primary analysis will be performed after the last participant has completed at least 15 months of follow-up from the first dose of study treatment or when 21 BI-EFS events have been observed, whichever occurs first.

    Measured: From the first dose of study treatment up to 2 years of follow-up

Secondary outcomes (9)

  1. Feasibility of observation vs consolidative RT (followed by maintenance pembrolizumab) in cCR patients after induction EVP: rate of cystectomy and/or muscle-invasive and non-muscle invasive recurrence per arm.

    Rate of cystectomy and/or muscle-invasive and non-muscle invasive recurrence per cCR treatment arm

    Measured: From cCR assesment until cystectomy and/or muscle-invasive or non-muscle-invasive recurrence, assessed up to 66 months.

  2. Overall survival (OS)

    OS is defined as the time between the date of enrollment and the date of death. OS will be estimated using the Kaplan-Meier method. The median OS and 95% confidence interval will be reported.

    Measured: From the date of enrollment until death from any cause, assessed up to 66 months.

  3. Progression-free survival (PFS)

    PFS is defined as time from start of therapy until an event or death by any cause

    Measured: From the first dose of study treatment until the first documented disease progression or death from any cause, assessed up to 66 months.

  4. Metastasis-free survival (MFS)

    • Time from start of therapy until occurrence of nodal or distant metastases, or progression of nodal metastases present at baseline by RECIST1.1 measurement

    Measured: From the first dose of study treatment until the first documented disease progression or death from any cause, assessed up to 66 months.

  5. Bladder function of no consolidation vs consolidative RT in cCR patients after induction EVP using bladder-specific QOL assessments.

    Bladder-specific quality of life assessed using the EORTC Quality of Life Questionnaire Core 30 (QLQ-C30; scores range 0-100; for functional scales, higher scores indicate better functioning; for symptom scales, higher scores indicate worse symptoms) and the EORTC Quality of Life Questionnaire Bladder Muscle Invasive (BLM-30 module, scores range 0-100; higher scores indicate [better/worse] outcome).

    Measured: At baseline C1D1, C3D1, Response Evaluation and 6, 12, 18 and 24 months after response evaluation, regardless of consolidative therapy

  6. Muscle-invasive recurrence in patients not undergoing cystectomy

    Measured in patients not undergoing a cystectomy, per relevant arm

    Measured: From cCR/non-CR assessment until muscle-invasive recurrence, assessed up to 66 months

  7. Non-muscle-invasive bladder recurrence in patients not undergoing cystectomy

    Measured in patients not undergoing a cystectomy, per relevant arm

    Measured: From cCR/non-CR assessment until non-muscle-invasive recurrence, assessed up to 66 months.

  8. Safety of EVP induction

    Safety in terms of immunotherapy-related adverse events by National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 criteria (NCI CTC-AE 5.0 criteria)

    Measured: After induction therapy: at a minimum of 22 months until up to 66 months of follow-up

  9. Prediction of BI-EFS by circulating tumor DNA (ctDNA) assessment

    ctDNA assessment in urine and plasma. Interim analysis is allowed

    Measured: From the date of enrollment until up to 66 months of follow-up

Timeline

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

  1. First posted23 Jun 2026
  2. Study start1 Sep 2026 (estimated)
  3. Primary completion1 Apr 2031 (estimated)
  4. Study completion1 Apr 2032 (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
Randomised
Intervention model
Parallel groups
Model description
All patients receive four 3-weekly cycles of induction therapy with Enfortumab Vedotin (Days 1 and 8) and Pembrolizumab (Day 1). After tumor assessment, patients are classified as clinical complete response (cCR) or non-cCR. Patients with cCR are randomized 1:1 to either no consolidation with maintenance pembrolizumab or consolidative radiotherapy followed by maintenance pembrolizumab. Patients with non-cCR are assigned to treatment arms based on their eligibility for bladder-sparing therapy. Patients with non-cCR who are eligible for bladder-sparing therapy will receive maintenance pembrolizumab following completion of bladder-sparing treatment. If these criteria are not met, patients will be advised to undergo radical cystectomy, followed by maintenance pembrolizumab. Further details on treatment arms and eligibility criteria are provided in the treatment arm specifications.
Masking
None (open label)
Enrolment
56 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07663747
Sponsor's protocol ID
M24FDL
Acronym
FIDELIO
Status last verified
Jun 2026
First submitted
28 Apr 2026
Last updated
25 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Enfortumab Vedotin, Pembrolizumab and Radiation in people with Urothelial Bladder Cancer, run by The Netherlands Cancer Institute at 3 sites in Netherlands.

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 22 inclusion and 34 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: opening soon, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Netherlands. 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?

Contact Michiel S van der Heijden, MD,PhD (+31205122671, ms.vd.heijden@nki.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Estimated 2-year bladder-intact event-free survival (BI-EFS) for the intention-to-treat population, measured from day 1 of treatment until the moment of analysis (time frame: From the first dose of study treatment up to 2 years of follow-up). 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 NCT07663747.

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 25 Jun 2026.

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