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

NCT05775471 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 22-001932NCI-2023-00999
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Renal Pelvis and Ureter Urothelial Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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.

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

• Radiographic recurrence-free survival

  From radical nephroureterectomy to 1 year

Secondary Outcomes (3)

• Incidence of adverse events

  Up to 30 days post treatment

• Rates of completion of neoadjuvant pembrolizumab and enfortumab vedotin

  Up to 3 years

• Perioperative complications

  Up to 30 days post- radical nephroureterectomy

Study Arms (1)

Treatment (pembrolizumab, enfortumab vedotin)

EXPERIMENTAL

Patients 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.

Procedure: Biopsy; Procedure: Biospecimen Collection; Drug: Enfortumab Vedotin; Procedure: MR Urography; Procedure: Nephroureterectomy; Biological: Pembrolizumab

Interventions

Biopsy PROCEDURE

Undergo tissue biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (pembrolizumab, enfortumab vedotin)

Biospecimen Collection PROCEDURE

Undergo blood and urine collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (pembrolizumab, enfortumab vedotin)

Enfortumab Vedotin DRUG

Given IV

Also known as: AGS 22ME, AGS-22M6E, Anti-Nectin 4 ADC ASG-22CE, Anti-nectin-4 Monoclonal Antibody-Drug Conjugate AGS-22M6E, ASG-22CE, Enfortumab Vedotin-ejfv, Padcev

Treatment (pembrolizumab, enfortumab vedotin)

MR Urography PROCEDURE

Undergo MRU

Also known as: Magnetic Resonance Urography

Treatment (pembrolizumab, enfortumab vedotin)

Nephroureterectomy PROCEDURE

Undergo nephroureterectomy

Also known as: Ureteronephrectomy

Treatment (pembrolizumab, enfortumab vedotin)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, enfortumab vedotin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator
• Seagen Inc.: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

RECRUITING

MeSH Terms

Interventions

Biopsy; Specimen Handling; enfortumab vedotin; Nephroureterectomy; pembrolizumab

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Nephrectomy; Urologic Surgical Procedures; Urogenital Surgical Procedures

Study Officials

• Karim Chamie

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ankush Sachdeva

CONTACT

310-794-3421; asachdeva@mednet.ucla.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2023
• First Posted: March 20, 2023
• Study Start: June 26, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 5, 2026

Record last verified: 2026-02

Locations

US (1)