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Renal Pelvis and Ureter Urothelial CarcinomaPhase 2NCT05775471

Pembrolizumab and Enfortumab Vedotin With Pembrolizumab Prior to and After Radical Nephroureterectomy for High-Risk Upper Tract Urothelial Cancer

A Phase 2 study testing Biopsy, Biospecimen Collection and Enfortumab Vedotin in people with Renal Pelvis and Ureter Urothelial Carcinoma, run by Jonsson Comprehensive 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
Search all trials

Trial summary

This phase II clinical trial tests how well pembrolizumab plus enfortumab vedotin prior to and after radical nephroureterectomy works in treating patients with high-risk upper tract urothelial cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy, Biospecimen Collection and Enfortumab Vedotin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
24 Jun 2024to 1 Jan 2028
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

  • Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of high-risk upper tract urothelial carcinoma will be enrolled in this study
  • Male participants: A male participant must agree to use a contraception during the treatment period and for at least 6 months after the last dose of study treatment and refrain from donating sperm during this period
  • Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
  • Not a woman of childbearing potential (WOCBP) OR
  • A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 6 months after the last dose of study treatment
  • Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue
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  • 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
  • Absolute neutrophil count (ANC) >= 1500/uL (Specimens must be collected within 10 days prior to the start of study intervention)
  • Platelets >= 100000/uL (Specimens must be collected within 10 days prior to the start of study intervention)
  • Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L (Specimens must be collected within 10 days prior to the start of study intervention)
  • Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance [CrCl]) (Specimens must be collected within 10 days prior to the start of study intervention) >= 30 mL/min for participant with creatinine levels > 1.5 x institutional ULN
  • Total bilirubin =<1.5 ×ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 × ULN (Specimens must be collected within 10 days prior to the start of study intervention)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) =< 2.5 x ULN (=< 5 x ULN for participants with liver metastases) (Specimens must be collected within 10 days prior to the start of study intervention)
  • International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (aPTT) =< 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants (Specimens must be collected within 10 days prior to the start of study intervention)

Who cannot join

  • A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
  • Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to allocation
  • Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to =< grade 1 or baseline. Participants with =< grade 2 neuropathy may be eligible. Participants with endocrine-related AEs grade =< 2 requiring treatment or hormone replacement may be eligible
  • Note: If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention
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  • Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=< 2 weeks of radiotherapy) to non-central nervous system (CNS) disease
  • Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist registered trademark) are live attenuated vaccines and are not allowed
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
  • 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
  • Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
  • Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention
  • Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a known history of Human Immunodeficiency Virus (HIV) infection. However, subjects who are on anti-retroviral therapy, have a viral load < 200 copies/milliliter, and CD4 count > 200/microliter, with a low risk of acquired immunodeficiency syndrome (AIDS)-related outcomes will be considered for enrollment.
  • Note: No HIV testing is required unless mandated by local health authority
  • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV ribonucleic acid [RNA] is detected) infection. Subjects who have underwent treatment with stable hepatitis B (defined as HBV deoxyribonucleic acid [DNA] < 500 IU/mL) are eligible. Patients with prior curative treatment of Hepatitis C virus are allowed if previously treated > 2 weeks prior to treatment initiation and HCV RNA undetectable by established laboratory values. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or 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
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment
  • Has had an allogenic tissue/solid organ transplant
  • Subjects who have previously received enfortumab vedotin or other MMAE-based ADCs
  • Subjects with an estimated life expectancy < 12 weeks
  • Subjects with known severe (>= grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin (including histidine, trehalose dihydrate, and polysorbate 20). Subjects with known severe (>= grade 3) hypersensitivity to any pembrolizumab excipient contained in the drug formulations of pembrolizumab
  • Subjects with another underlying medical condition that, in the opinion of the investigator, would impair the ability of the subject to receive or tolerate the planned treatment and follow-up; any known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
  • Subjects with active keratitis or corneal ulcerations. Subjects with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator

Trial locations and contacts

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

Ankush Sachdeva contact

310-794-3421

asachdeva@mednet.ucla.edu

United States1 site, 1 recruiting

  • UCLA / Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

    Ankush Sachdeva, 310-794-3421, asachdeva@mednet.ucla.edu

    Karim Chamie

    Recruiting

Other trials in United States

About this study

Official title: Neoadjuvant Combination Pembrolizumab / Enfortumab Vedotin With Adjuvant Pembrolizumab Prior to and After Radical Nephroureterectomy for High-Risk Upper Tract Urothelial Carcinoma

This phase II clinical trial tests how well pembrolizumab plus enfortumab vedotin prior to and after radical nephroureterectomy works in treating patients with high-risk upper tract urothelial cancer. 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. Enfortumab vedotin (EV) 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. Radical nephroureterectomy (RNU) is the surgical removal of a kidney and its ureter. Giving pembrolizumab plus enfortumab vedotin before surgery may make the tumor smaller and may reduce the amount of normal tissue that needs to be removed and giving pembrolizumab after surgery may kill any remaining cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess pathologic objective response rate (ORR; complete response [CR; pT0] and partial response [PR; < pT2] rate) at the time of radical nephroureterectomy.

II. To assess recurrence-free survival post radical nephroureterectomy.

SECONDARY OBJECTIVE:

  1. To describe the side effect profile, tolerability, and surgical complications in patients receiving neoadjuvant pembrolizumab (pembro)/ enfortumab vedotin (EV) prior to RNU.

EXPLORATORY OBJECTIVE:

  1. Correlative studies will evaluate the predictive potential of imaging and ureteroscopic response (visualization of tumor, biopsy, and cytology), and urinary, serum, and tissue biomarkers to pathologic response.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) and enfortumab vedotin IV on study. Patients undergo radical nephroureterectomy and receive pembrolizumab IV on study Patients also undergo magnetic resonance urogram (MRU) imaging and undergo blood, urine and tissue sample collection throughout the study.

Being tested
Biopsy, Biospecimen Collection, Enfortumab Vedotin, MR Urography, Nephroureterectomy

What participants receive

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

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo tissue biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood and urine collection

  • 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

  • MR UrographyProcedure or surgery

    Also called Magnetic Resonance Urography

    Undergo MRU

  • NephroureterectomyProcedure or surgery

    Also called Ureteronephrectomy

    Undergo nephroureterectomy

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT05775471
Study groupRoleWhat they receive
Treatment (pembrolizumab, enfortumab vedotin)ExperimentalPatients receive pembrolizumab IV and enfortumab vedotin IV on study. Patients undergo radical nephroureterectomy and receive pembrolizumab IV on study Patients also undergo MRU imaging and undergo blood, urine and tissue sample collection throughout the study.
Receives: Procedure: Biopsy; Procedure: Biospecimen Collection; Drug: Enfortumab Vedotin; Procedure: MR Urography; Procedure: Nephroureterectomy; Biological: Pembrolizumab

What is being measured

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

  1. Pathological objective response (ORR) rate

    Will be assessed by the combination of partial response (PR) and complete response (CR). PR is defined as pathologic stage <T2 disease. CR is defined as pT0 disease and assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.

    Measured: from radical nephroureterectomy through study completion, an average of 1 year

  2. Radiographic recurrence-free survival

    Measured: From radical nephroureterectomy to 1 year

Secondary outcomes (3)

  1. Incidence of adverse events

    Will be assessed using the National Cancer Institute, Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0.

    Measured: Up to 30 days post treatment

  2. Rates of completion of neoadjuvant pembrolizumab and enfortumab vedotin

    Will be assessed as completion of all infusions of both agents and successful completion of radical nephroureterectomy.

    Measured: Up to 3 years

  3. Perioperative complications

    Will be assessed based on the Clavien-Dindo classification.

    Measured: Up to 30 days post- radical nephroureterectomy

Timeline

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

  1. First posted20 Mar 2023
  2. Study start24 Jun 2024
  3. Primary completion1 Jan 2027 (estimated)
  4. Study completion1 Jan 2028 (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
21 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05775471
Sponsor's protocol ID
22-001932
Other IDs
NCI-2023-00999
Status last verified
Feb 2026
First submitted
6 Mar 2023
Last updated
16 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biopsy, Biospecimen Collection and Enfortumab Vedotin in people with Renal Pelvis and Ureter Urothelial Carcinoma, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

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 14 inclusion and 28 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: looking for participants now, as of the sponsor's last update on 16 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 Ankush Sachdeva (310-794-3421, asachdeva@mednet.ucla.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological objective response (ORR) rate (time frame: from radical nephroureterectomy through study completion, an average of 1 year). The study lists 2 primary outcomes in all. 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 NCT05775471.

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 16 Jul 2026.

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