N-803 in Combination With Pembrolizumab and Enfortumab Vedotin for Treatment of Urothelial Cancer

NCT07217496 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: ResQ523NCI-2025-07330
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial will investigate the effect of N-803 in combination with pembrolizumab and enfortumab vedotin in treating participants with urothelial cancer 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).

Conditions

Urothelial Carcinoma; Locally Advanced Urothelial Carcinoma; Urothelial Cancer; Metastatic Urothelial Carcinoma; Bladder Cancer

Outcome Measures

Primary Outcomes (2)

• Assess the safety and tolerability of the treatment regimen (NAI, EV, and pembrolizumab).

  The proportion of participants with treatment-emergent adverse events (TEAEs), as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.

  From the date of first dose of study product to 30 days after the last dose of study product.

• 12-month progression-free survival (PFS) of participants with locally advanced or metastatic urothelial carcinoma (mUC) receiving EV plus pembrolizumab and NAI

  Percentage of participants alive and progression free at 12 months, defined as the time from the date of first dose of study drugs (C1D1) to the date of disease progression or death (any cause), whichever occurs first, by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

  From the date of first dose of study drugs to the date of disease progression or death (any cause)

Secondary Outcomes (2)

• To evaluate the preliminary efficacy of the treatment regimen (EV, pembrolizumab, and NAI)

  12 months

• To evaluate PFS, ORR, DOR, and CBR using immune RECIST (iRECIST).

  From date of first dose of study drugs to the end of the follow up period, up to five years.

Study Arms (1)

Treatment

EXPERIMENTAL

Participants will start combined treatment with EV/Pembrolizumab (P) and NAI. Treatment will consist of up to 12 cycles of EV and up to 35 cycles of NAI and pembrolizumab (2 years).

Drug: Nogapendekin Alfa Inbakicept (NAI); Drug: enfortumab vedotin (EV); Drug: Pembrolizumab

Interventions

enfortumab vedotin (EV) DRUG

1.25 mg/kg given intravenously (IV) on Day 1 and Day 8 of each 3-week cycle, for approximately 5.5 to 8 months (8 to 12 cycles), but no more than 12 cycles.

Also known as: Enfortumab Vedotin, Padcev

Treatment

Pembrolizumab DRUG

200 mg given intravenously (IV) every 3 weeks, for a maximum of 35 cycles (2 years)

Also known as: Keytruda

Treatment

Nogapendekin Alfa Inbakicept (NAI) DRUG

1.2mg given subcutaneously (SC) every 3 weeks, for a maximum of 35 cycles (2 years). Known HIV-positive participants will receive a weight-based dose of 6 µg/kg

Also known as: ANKTIVA, NAI, N-803

Treatment

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old.
• Histologically or cytologically confirmed locally advanced/ mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra. Mixed-cell type tumors are eligible as long as \>50% urothelial component is present (mixed histology other than small cell/ neuroendocrine are allowed).
• No prior systemic treatment for locally advanced/mUC.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
• Measurable disease according to RECIST v1.1.
• Prior perioperative systemic therapy including neoadjuvant or adjuvant chemotherapy, immune checkpoint inhibitors, and EV is allowed if treatment was completed \>12 months before trial enrollment.
• Participants enrolling in the trial must agree with discontinuing EV upon demonstrating confirmed CR/PR/SD at the second or third scan timepoint on treatment (after 5.5 to 8 months of intended EV treatment).
• Adequate organ and marrow function as defined below:
• Leukocytes ≥ institutional lower limit of normal (LLN)
• Absolute neutrophil count (ANC) ≥ 1,500/μL
• Platelets ≥ 100,000/μL
• Total bilirubin \< 1.5 × institutional upper limit of normal (ULN) (if previously abnormal due to non-malignant causes such as Gilbert's disease bilirubin ≤ 2 × ULN will be permitted.)
• Aspartate aminotransferase (AST) (SGOT)/ alanine aminotransferase (ALT) (SGPT) ≤ 2.5 × institutional upper limit of normal (ULN)
• Creatinine clearance ≥ 30 mL/min/1.73 m2 calculated using the Cockcroft-Gault equation
• Must have archival tumor tissue available or have disease amenable to a fresh biopsy for diagnosis confirmation and correlative studies.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Symptomatic or untreated central nervous system (CNS) metastases. Note: Participants with previously treated brain or CNS metastases are eligible if the participant have recovered from any acute effects of surgery or radiotherapy and do not require steroids (prednisone equivalent ≥ 10 mg daily), and any whole brain radiation therapy or any stereotactic radiosurgery was completed at least 2 weeks prior to initiation of therapy.
• History of active autoimmune disease and on active management with immunosuppressive agents within the past 2 years.
• History of interstitial lung disease.
• Congestive heart failure (New York Heart Association class III or IV)
• Participants on systemic intravenous (IV) or oral corticosteroid therapy (prednisone equivalent ≥ 10 mg daily) or other immunosuppressive agents such as azathioprine or cyclosporin A. For these participants, these excluded treatments must be discontinued at least 1 week prior to enrollment for recent short course use (≤ 14 days) or discontinued at least 4 weeks prior to enrollment for long term use (\> 14 days).
• Note: The use of corticosteroids as premedication for contrast-enhanced studies is allowed prior to enrollment and on study. Participants requiring hormone replacement with corticosteroids if the steroids are administered only for the purpose of hormonal replacement or participants treated at doses ≤ 10 mg of prednisone or equivalent per day are allowed.
• History of uncontrolled diabetes mellitus defined as hemoglobin A1c (HbA1c) ≥ 8%.
• Grade ≥ 2 peripheral neuropathy at baseline.
• Radiotherapy or major surgery within 2 weeks prior to treatment start.
• History of another significant life-limiting malignancy within 2 years prior to the first dose of study drug. Participants with nonmelanoma skin cancer, curatively treated localized prostate cancer, or carcinoma in situ of any type (if complete resection was done) are allowed.
• History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to EV and/or pembrolizumab and/or NAI.
• Received hematopoietic stem cell transplantation or solid organ transplantation.
• Known active keratitis or corneal ulcerations.
• Received or will receive a live vaccine within 30 days prior to the first administration of study intervention.

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms

Interventions

ALT-803; enfortumab vedotin; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Central Study Contacts

Kayleigh Russell

CONTACT

424-539-2412; kayleigh.russell@immunitybio.com

Mark Nelson

CONTACT

mark.nelson@immunitybio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2025
• First Posted: October 16, 2025
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2032
• Last Updated: September 24, 2026

Record last verified: 2026-08

Locations

US (1)