A Study of Enfortumab Vedotin in People With Urothelial Carcinoma of the Upper Urinary Tract

NCT05868265 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 21-393
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to find out whether the study drug, enfortumab vedotin, is an effective and safe treatment for people who have urothelial carcinoma of the upper urinary tract. Study participants will be people who are not eligible to receive or have chosen not to receive the chemotherapy drug cisplatin for treatment of their cancer. In addition, all participants will be planning on having standard surgery to remove their tumor.

Conditions

Urothelial Carcinoma

Keywords

Enfortumab Vedotin; Upper Urinary Tract; High Grade; Radical surgery + pelvic lymph node dissection; 21-393

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who achieve pathologic complete response

  The absence of residual disease on pathologic evaluation on surgical specimen following neoadjuvant enfortumab vedotin for UTUC. Pathologists will assess surgical specimens systematically using criteria agreed upon for all conventional neoadjuvant treatment based on the AJCC TNM staging system.

  up to 2 years

Secondary Outcomes (1)

• The rate of grade 3 - 4 toxicity

  up to 2 years

Study Arms (1)

Enfortumab Vedotin

EXPERIMENTAL

All patients will receive enfortumab vedotin at 1.25 mg/kg on days 1 and 8 of 21 days cycle, for a total of three cycles, followed by radical nephroureterectomy, ureterectomy, or nephrectomy, depending on the site of the tumor and per the clinical decision of the treating urologist.

Drug: Enfortumab Vedotin; Procedure: Radical surgery

Interventions

Enfortumab Vedotin DRUG

All patients will receive enfortumab vedotin at 1.25 mg/kg on days 1 and 8 of 21 days cycle, for a total of three cycles.

Enfortumab Vedotin

Radical surgery PROCEDURE

Radical surgery, such as radical nephroureterectomy, nephrectomy or ureterectomy is to take place within 60 days from the last dose of treatment end of cycle 3 (i.e., cycle 3 day 22).

Enfortumab Vedotin

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed high grade urothelial carcinoma of the upper tract and/or radiographically visible tumor stage T2-T4a N0/x M0 disease with positive selective urinary cytology. Hydronephrosis associated with tumor on imaging or biopsy will be considered invasive by definition. (Variant histology is acceptable if there is a predominant urothelial component. Discussion with PI strongly encouraged.) Retroperitoneal lymph nodes \<15 mm in the short axis will be eligible.
• Patients who are
• o Ineligible for cisplatin based on any of the following criteria:
• Estimated or calculated creatinine clearance ≥ 30ml/min but \< 60 ml/min
• Grade 2 or above audiometric hearing loss (per CTCAE v5.0) or
• Declined cisplatin-based neoadjuvant chemotherapy, as documented in medical chart
• Availability of tumor specimen block, cell block or 30 unstained slides from diagnosis. Patients with fewer than 30 slides available may be enrolled after discussion with the Principal Investigator.Additional research biopsy is not required.
• Karnofsky performance status ≥ 70%.
• Medically appropriate candidate for radical surgery (nephroureterectomy, nephrectomy, or ureterectomy), as per treating Attending Urologic Oncologist
• Age ≥ 18 years.
• Required initial laboratory values:
• Absolute neutrophil count ≥ 1.5 x 10\^9 /L
• Platelets ≥ 100 x 109 /L
• Bilirubin ≤1.5 times the upper limit of normal (x ULN)
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN PTT/PT ≤1.5 x ULN or INR \< 1.7 x ULN for patients who are not receiving therapeutic anticoagulation. Patients receiving therapeutic anticoagulation should be on a stable dose

You may not qualify if:

• Presence of metastatic disease.
• Prior treatment with systemic chemotherapy or radiotherapy for urothelial cancer of the bladder within the last 2 years. (Prior intravesical treatment such as BCG is allowed).
• Grade 2 or higher peripheral neuropathy.
• Patients with active keratitis or corneal ulcerations. Patients with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator.
• Patients with uncontrolled diabetes. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c 7% to \<8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
• Unstable angina.
• New York Heart Association (NYHA) Grade II or greater congestive heart failure.
• History of myocardial infarction within 6 months.
• History of stroke within 6 months.
• Evidence of bleeding diathesis or coagulopathy. Therapeutic anticoagulation is permitted, but patients must be on a stable dose.
• Major surgical procedure within 28 days prior to the study. (Transurethral resection of bladder tumor is permitted)
• Serious, non-healing wound, ulcer, or bone fracture.
• Patients with active tuberculosis.
• Other prior malignancy active within the previous 2 years except for local or organ confined early stage cancer that has been definitively treated with curative intent or does not require treatment, does not require ongoing treatment, has no evidence of active disease, and has a negligible risk of recurrence and is therefore unlikely to interfere with the endpoints of the study.
• Prior treatment with enfortumab vedotin or other MMAE-based antibody-drug conjugates (ADCs).

Sponsors & Collaborators

• Astellas Pharma US, Inc.: collaborator
• Memorial Sloan Kettering Cancer Center: lead

Study Sites (8)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk - Commack (Limited protocol activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

University of Rochester Medical Center (Data Collection Only)

Rochester, New York, 14642, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited protocol activities)

Uniondale, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

enfortumab vedotin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Scot Niglio, MD, MS

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Scot Niglio, MD, MS

CONTACT

646-888-4867; niglios@mskcc.org

Jonathan Rosenberg, MD

CONTACT

646-422-4461

Study Design

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

Model Details: This is a single arm phase II trial.

Study Record Dates

• First Submitted: May 11, 2023
• First Posted: May 22, 2023
• Study Start: June 2, 2023
• Primary Completion (Estimated): June 2, 2027
• Study Completion (Estimated): June 2, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (8)