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Locally Advanced Bladder Urothelial CarcinomaPhase 1/2NCT07667335

Enfortumab Vedotin, Pembrolizumab and Quemliclustat for the Treatment of Unresectable Locally Advanced and Metastatic Urothelial Cancer

A Phase 1/2 study testing Quemliclustat, Biospecimen Collection and Computed Tomography in people with Locally Advanced Bladder Urothelial Carcinoma and Locally Advanced Renal Pelvis Urothelial Carcinoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record

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Trial summary

This phase Ib/II trial tests the safety, side effects, and best dose of quemliclustat in combination with enfortumab vedotin and pembrolizumab, and to see how well the combination works for the treatment of bladder, renal pelvis, or ureter urothelial cancer that cannot be removed by surgery (unresectable), that has… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Quemliclustat, Biospecimen Collection and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteUnited States
Study dates
20 Oct 2026to 16 Jul 2029
Phase
Phase 1/2

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 must be at least 18 years of age on the day of signing informed consent. Participant provides written informed consent for trial
  • Participants must have previously untreated locally advanced or metastatic bladder cancer including bladder cancer [stage IIIB: T1-T4N2-3M0, stage IVa: T4bAnyNM0 or AnyTAnyNM1a, and stage IVB: AnyTAnyNM1b clinical stage per American Joint Commission on Cancer (AJCC)] or renal pelvis or ureter cancer [stage IV: T4Nx-0M0, AnyTN1-2M0, AnyTAnyNM1 clinical stage per AJCC]. Lymph node with ≥ 15 mm short axis or biopsy-positive for carcinoma will be considered pathologically enlarged and measurable
  • Participants must have either conventional urothelial carcinoma or urothelial carcinoma variants. A review of pathology by a local expert genitourinary (GU) pathologist is required to confirm the diagnosis. Any component (%) of non-conventional urothelial noted on tumor specimen is allowed for only histologic subtypes listed below in up to 20% of participants enrolled in this study.
  • Urothelial carcinoma with squamous differentiation
  • Urothelial carcinoma with glandular differentiation
  • Urothelial carcinoma with trophoblastic differentiation
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  • Nested urothelial carcinoma
  • Tubular and microcystic urothelial carcinoma
  • Micropapillary urothelial carcinoma
  • Lymphoepithelioma-like urothelial carcinoma
  • Plasmacytoid urothelial carcinoma
  • Sarcomatoid urothelial carcinoma
  • Giant cell urothelial carcinoma
  • Lipid-rich urothelial carcinoma
  • Clear cell (glycogen rich) urothelial carcinoma
  • Poorly differentiated urothelial carcinoma
  • Squamous cell neoplasms including pure squamous cell carcinomas, verrucous carcinomas and squamous cell papilloma
  • Measurable disease by RECIST v 1.1
  • Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2
  • Available baseline fresh biopsy tissue sample obtained in the protocol RG1712006 or RG1125031 though clinically indicated procedures or participants must be willing to undergo a baseline research biopsy when safe and feasible
  • Participant must have an estimated life expectancy of at least 3 months
  • Hemoglobin ≥ 9 g/dl
  • Absolute neutrophil count: ≥ 1500/ µL
  • White blood cell count: ≥ 3000/µL
  • Absolute lymphocyte count: ≥ 1000/µL
  • Platelet count: ≥ 100.000/µL (without transfusion support)
  • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤ 2.5 x upper limit of normal (ULN)
  • Total bilirubin: ≤ 1.5 mg/dl except for patients with Gilbert's syndrome who must have a total bilirubin ≤ 3 mg/dl
  • Creatinine clearance: ≥ 30 ml/min/1.73m^2 by the method of Chronic Kidney Disease Epidemiology Collaboration (CKI-EPI) or ≥ 30 ml/min by the method of 24 hour (h) clearance of creatinine calculation
  • International Normalized Ratio (INR): < 1.5

Who cannot join

  • Participants who are receiving any other investigational agents or concurrent anticancer treatment. Participants must have adequate treatment washout period before treatment, defined as: Major surgery (≥ 4 weeks), palliative radiation therapy (≥ 1 weeks from completion of treatment if they have recovered from the acute toxic effect of radiotherapy), prior adjuvant immunotherapy (≥ 4 weeks)
  • Participants whose tumors have any % neuroendocrine or small cell histology, glandular neoplasms, urachal carcinomas, tumor of mullerian type, mesenchymal tumors or urothelial tract hematopoietic and lymphoid tumors
  • Participants considered to be medically unfit for EV-P regimen as per Investigator discretion
  • Participants with concurrent use of systemic steroids (within 10 days of enrollment), except for physiologic doses of systemic steroid replacement or local (topical, nasal, intraarticular or inhaled) steroid use
  • Participants who have experienced disease progression following neoadjuvant or adjuvant systemic therapy within 12 months prior to enrollment will not be eligible
  • Patients with Fridericia's corrected QT interval (QTcF) interval at screening of > 480 milliseconds.
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  • Note: For any QTcF > 480 milliseconds on initial electrocardiogram (ECG), a follow-up ECG will be performed to confirm QTcF interval prolongation and exclude the patient from this study
  • Participants with active systemic autoimmune disease (e.g., lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma, inflammatory bowel disease). Participants with autoimmune endocrine disorders controlled by medical management (e.g. thyroid disorders, type 1 diabetes, or adrenal insufficiency) will not be excluded
  • Participants who are known to be serologically positive for human immunodeficiency virus (HIV) and a CD4 count < 350 cells/microliter
  • Participants with known active hepatitis (i.e. Hepatitis B or C). Prior hepatitis (Hep) C infection is allowed as long as polymerase chain reaction (PCR) test is negative
  • Participants with clinically inactive brain metastases may be included. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole-brain radiation therapy and study treatment
  • Participants with new or progressive brain metastases (less or equal of 1 cm of larger diameter) are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the participant and the investigator favors participation in the clinical trial. Patients with leptomeningeal disease will be excluded
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
  • Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy of assessment of the investigational regimen are eligible for this trial
  • Woman of childbearing potential with positive serum pregnancy test within 72 hours prior to enrollment. Active lactation is an exclusion criterion

Trial locations and contacts

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

Rosa Nadal Rios, MD, PhD contact

206-598-3300

rnadalri@fredhutch.org

United States1 site, 1 recruiting

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

    Rosa Nadal Rios, MD, PhD, 206-598-3300, rnadalri@fredhutch.org

    Rosa Nadal Rios, MD, PhD

    Recruiting

Other trials in United States

About this study

Official title: A Phase Ib/II Study to Evaluate the Safety and Efficacy of Enfortumab Vedotin Plus Pembrolizumab in Combination With Quemliclustat in Unresectable Locally Advanced and Metastatic Urothelial Carcinoma

This phase Ib/II trial tests the safety, side effects, and best dose of quemliclustat in combination with enfortumab vedotin and pembrolizumab, and to see how well the combination works for the treatment of bladder, renal pelvis, or ureter urothelial cancer that cannot be removed by surgery (unresectable), that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of cancer cells. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Quemliclustat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving quemliclustat in combination with enfortumab vedotin and pembrolizumab and may be safe, tolerable and/or effective in treating patients with unresectable locally advanced and metastatic urothelial cancer.

Read the detailed description

OUTLINE:

Patients receive quemliclustat intravenously (IV) on day 1, enfortumab vedotin IV on days 1 and 8 and pembrolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy during screening and optionally undergo throughout the study. Patients also undergo computed tomography (CT)/magnetic resonance imaging (MRI) and blood sample collection throughout the study.

After completion of study treatment, patients are followed up within 30 days and then every 12 weeks for 3 years.

Being tested
Quemliclustat, Biospecimen Collection, Computed Tomography, Enfortumab Vedotin, Magnetic Resonance Imaging
Medical subject headings
Urinary Bladder Neoplasms, Ureteral Neoplasms

What participants receive

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

  • QuemliclustatDrug

    Also called AB 680, AB-680, AB680, CD73 Inhibitor AB680

    Given IV

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • Enfortumab VedotinDrug

    Also called AGS 22ME, AGS-22M6E, Anti-Nectin 4 ADC ASG-22CE, Anti-nectin-4 Monoclonal Antibody-Drug Conjugate AGS-22M6E

    Given IV

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • PembrolizumabBiological

    Also called BCD-201, GME 751, GME751, Keytruda

    Given IV

  • Biopsy ProcedureProcedure or surgery

    Also called Bx, BIOPSY_TYPE

    Undergo tumor biopsy

Study groups in NCT07667335
Study groupRoleWhat they receive
Treatment (enfortumab vedotin, pembrolizumab, quemliclustat)ExperimentalPatients receive quemliclustat IV on day 1, enfortumab vedotin IV on days 1 and 8 and pembrolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy during screening and optionally undergo throughout the study. Patients also undergo CT/MRI and blood sample collection throughout the study.
Receives: Drug: Quemliclustat; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Enfortumab Vedotin; Procedure: Magnetic Resonance Imaging; Biological: Pembrolizumab; Procedure: Biopsy Procedure

What is being measured

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

  1. Incidence of treatment related adverse events (Phase Ib)

    As measured by Common Terminology Criteria for Adverse Events version (v) 6.

    Measured: From baseline, up to 21 days after last dose of investigational product

  2. Overall response rate (ORR) (Phase II)

    Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. Will calculate the count and percentage with a 95% confidence interval (CI).

    Measured: From baseline, up to disease progression or unacceptable side effects, up to 3 years after completion of study treatment

Secondary outcomes (5)

  1. ORR (Phase Ib)

    Assessed by RECIST v 1.1. Will calculate the count and percentage with a 95% CI.

    Measured: From baseline, up to disease progression or unacceptable side effects, up to 3 years after completion of study treatment

  2. Complete response rate (Phase II)

    Assessed by RECIST v 1.1. Will calculate the count and percentage with a 95% CI.

    Measured: From baseline, up to disease progression or unacceptable side effects, up to 3 years after completion of study treatment

  3. Duration of response (Phase II)

    Will use Kaplan Meier method to estimate the survival curve, median and its corresponding 95% CI.

    Measured: From response (ORR) until disease progression or unacceptable side effects or death which occurs earlier, up to 3 years after completion of study treatment

  4. Progression free survival (Phase II)

    Will use Kaplan Meier method to estimate the survival curve, median and its corresponding 95% CI.

    Measured: From date of registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, up to 3 years after completion of study treatment

  5. Rate of consolidative therapy with cystectomy or chemoradiation with stage 3b (Phase II)

    Will calculate the count and percentage with a 95% CI.

    Measured: Up to 6 months

Timeline

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

  1. First posted25 Jun 2026
  2. Study start20 Oct 2026
  3. Primary completion16 Jul 2029 (estimated)
  4. Study completion16 Jul 2029 (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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07667335
Sponsor's protocol ID
RG1125912
Other IDs
NCI-2026-03972, FHIRB0021336
Status last verified
Sep 2026
First submitted
18 Jun 2026
Last updated
22 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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