Metastatic Urothelial CarcinomaPhase 1NCT07217496
N-803 in Combination With Pembrolizumab and Enfortumab Vedotin for Treatment of Urothelial Cancer
A Phase 1 study testing Nogapendekin Alfa Inbakicept (NAI), enfortumab vedotin (EV) and Pembrolizumab in people with Metastatic Urothelial Carcinoma and Urothelial Carcinoma, run by ImmunityBio, Inc. at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Urothelial Carcinoma, Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma
- What is being tested?
- Nogapendekin Alfa Inbakicept (NAI), enfortumab vedotin (EV) and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2026to Jan 2032
- Phase
- Phase 1
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
- 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.
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- 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.
- Human immunodeficiency virus (HIV)-infected individuals with undetectable viral load within 6 months are eligible for this trial. Trial participants who are on antiretroviral therapy (ART) should be on established ART for at least 4 weeks and have an HIV viral load less than 400 copies/mL prior to enrollment.
- For participants with history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable, and the participant should be on suppressive antiviral therapy, if indicated. Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured, with HCV viral load below the level of quantification. A participant who is HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution is eligible for this trial. For individuals with HCV infection who are currently on treatment, they are eligible if HCV viral load is below the level of quantification.
- Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
- Participants who are on beta blockers can enroll in the trial, but discontinuation of beta-blockers should be strongly considered at the time of initiating NAI. Beta blocker use can continue per physician discretion if necessary.
- Agreement to practice effective contraception for female participants of childbearing potential and nonsterile males. Female participants of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Female participants of childbearing potential must have a negative pregnancy test and adhere to using a highly effective method of contraception (refer to Section 4.1.3) prior to screening and agree to continue its use during the study or be surgically sterilized (eg, hysterectomy) while on study and for 7 months post last dose of study drug. Male participants must agree to use barrier methods of birth control while on study and to advise their female partners to use a highly effective method of contraception for 7 months post last dose of study drug.
- Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
Who cannot join
- 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).
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- 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.
- Note: Seasonal flu vaccines that do not contain a live virus are permitted. Locally approved COVID-19 vaccines are permitted.
- Pregnant and nursing women.
- Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
- Severe uncontrolled intercurrent illness that would limit compliance with study requirements in the judgement 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.
Mark Nelson contact
United States1 site
University of California, San Francisco
San Francisco, California, 94143
UCSF Genitourinary Medical Oncology Recruitment, 877-827-3222, GUTrials@ucsf.edu
About this study
Official title: Open-Label, Single-Arm, Phase 1b Clinical Trial of NAI Plus Pembrolizumab With Short Course of Enfortumab Vedotin in Treatment-Naïve Participants With Metastatic Urothelial Carcinoma
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).
Read the detailed description
This is an open label, phase 1b single arm trial with a safety lead-in cohort to determine the preliminary efficacy and safety of EV plus pembrolizumab and NAI in participants with unresectable locally advanced or mUC who are treatment-naïve in the metastatic setting.
- Conditions
- Metastatic Urothelial Carcinoma, Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Urothelial Cancer, Bladder Cancer
- Being tested
- Nogapendekin Alfa Inbakicept (NAI), enfortumab vedotin (EV), Pembrolizumab
- Medical subject headings
- Carcinoma, Transitional Cell, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nogapendekin Alfa Inbakicept (NAI)Drug
Also called ANKTIVA, NAI, N-803
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
enfortumab vedotin (EV)Drug
Also called Enfortumab Vedotin, Padcev
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.
PembrolizumabDrug
Also called Keytruda
200 mg given intravenously (IV) every 3 weeks, for a maximum of 35 cycles (2 years)
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Nogapendekin Alfa Inbakicept (NAI); Drug: enfortumab vedotin (EV); Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
To evaluate the preliminary efficacy of the treatment regimen (EV, pembrolizumab, and NAI) as measured by complete response rate (CRR), objective response rate (ORR), clinical benefit rate (CBR), 12-month overall survival (12-OS), median duration of response (mDOR), median progression free survival (mPFS) and median overall survival (mOS).
Measured: 12 months
To evaluate PFS, ORR, DOR, and CBR using immune RECIST (iRECIST).
PFS will be defined as the time from the date of first dose of study drugs (C1D1) to the date of disease progression or death (any cause), by RECIST v1.1 whichever occurs first. ORR is defined as the portion of participants who experience an objective response (confirmed CR or confirmed PR) per RECIST v1.1. DOR will be defined as the time from the first date of documented response (confirmed CR or confirmed PR) to the date of disease progression or death (any cause), by RECIST v1.1 whichever occurs first. CBR is defined as the portion of participants who experience clinical benefit (confirmed CR, confirmed PR, or SD for at least 24 weeks) per RECIST v1.1.
Measured: From date of first dose of study drugs to the end of the follow up period, up to five years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2025
- Study startDec 2026 (estimated)
- Primary completionJan 2028 (estimated)
- Study completionJan 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Urothelial CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ImmunityBio, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07217496
- Sponsor's protocol ID
- ResQ523
- Other IDs
- NCI-2025-07330
- Status last verified
- Aug 2026
- First submitted
- 14 Oct 2025
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided