VSV-IFNβ-NIS With Ipilimumab and Nivolumab for the Treatment of Advanced or Metastatic Clear Cell Renal Cell Carcinoma

March 30, 2026 updated by: Mayo Clinic

Phase 2 Clinical Evaluation of Combination Immunotherapy for Renal Cell Carcinoma

This phase II trial tests adding VSV-IFNβ-NIS to standard of care ipilimumab and nivolumab for the treatment of clear cell renal cell carcinoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). A virus modified in the laboratory, such as VSV-IFNβ-NIS, may be able to kill tumor cells without damaging normal cells. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving VSV-IFNβ-NIS with ipilimumab and nivolumab may be effective for the treatment of advanced or metastatic clear cell renal cell carcinoma.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

18

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester
        • Contact:
        • Principal Investigator:
          • Brian A. Costello, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 18 years

  • Disease Characteristics:

    • Histological confirmation of advanced (not amenable to curative surgery or radiation therapy) or metastatic [American Joint Committee on Cancer (AJCC) version 8 Stage IV] renal cell carcinoma (RCC) with a clear cell component, including all International Metastatic RCC Database Consortium (IMDC) risk categories (favorable, intermediate, and poor risk) allowed

  • Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

    • NOTE: Liver lesions that have been previously embolized (bland embolization, chemo- or radio-embolization) or have undergone percutaneous thermoablation are not eligible as target lesions. Tumor lesions in a previously irradiated area are not considered measurable disease; disease that is measurable by physical examination only is not eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • Hemoglobin ≥ 9.0 g/dL (obtained ≤ 15 days prior to registration)
  • Absolute neutrophil count (ANC) ≥ 1500/mm^3 (obtained ≤ 15 days prior to registration)
  • Platelet count ≥ 100,000/mm^3 (obtained ≤ 15 days prior to registration)
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 15 days prior to registration)
  • Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 15 days prior to registration)
  • Prothrombin time (PT)/international normalization ratio (INR)/activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 15 days prior to registration)

  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance ≥ 50 ml/min using the chronic kidney disease epidemiology (CKD-EPI) creatinine equation (per National Kidney Foundation) (obtained ≤ 15 days prior to registration)

    • NOTE: See calculator at National Kidney Foundation website here: https://www.kidney.org/professionals/kdoqi/gfr_calculator
  • Negative pregnancy test done ≤ 8 days prior to registration, for persons of childbearing potential only
  • Provide written informed consent
  • Willingness to provide mandatory blood specimens for correlative research
  • Willingness to provide mandatory tissue specimens for correlative research
  • Willing to return to Mayo Clinic for follow-up (during the active monitoring phase of the study)

Exclusion Criteria:

  • Any of the following because this study involves an investigational agent, the genotoxic, mutagenic and teratogenic effects of which on the developing fetus and newborn are unknown:

    • Pregnant persons
    • Nursing persons
    • Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception
  • Prior treatment for advanced or metastatic RCC [American Joint Committee on Cancer (AJCC) Stage IV]

  • History of portal vein thrombosis involving more than intrahepatic portal vein branches: thrombosis of the right or left portal vein branch or the bifurcation, partial or complete obstruction of the portal vein trunk

    • NOTE: Level 0 or 1 tumor thrombus remain eligible; Level 2, 3, of 4 tumor thrombus related to the primary kidney tumor are ineligible

  • Has received a live vaccine ≤ 30 days prior to registration

    • NOTE: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are NOT allowed

  • Any of the following prior therapies:

    • Surgery ≤ 3 weeks prior to registration
    • Chemotherapy ≤ 2 weeks prior to registration
    • Radiation therapy ≤ 2 weeks prior to registration
    • Therapy in the first-line setting for advanced or metastatic RCC
    • Adjuvant immunotherapy during which or in the ≤ 6 months immediately following, relapse or disease progression has occurred
  • New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or known cardiac arrhythmias [atrial fibrillation or supraventricular tachycardia (SVT)]
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

  • Uncontrolled intercurrent illness including, but not limited to:

    • ongoing or active infection
    • symptomatic congestive heart failure
    • unstable angina pectoris
    • cardiac arrhythmia
    • dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
    • or psychiatric illness/social situations that would limit compliance with study requirements

  • Current immunodeficiency or immunosuppression and receiving systemic corticosteroids at > 10mg/day prednisone or equivalent ≤ 1 week prior to registration.

    • NOTE: Inhaled steroids for pulmonary disease are permitted

  • Known history of the following:

    • Suspected active organ-threatening autoimmune disease including, but not limited to, inflammatory bowel disease, autoimmune hepatitis, lupus, or pneumonitis which can flare while receiving immune checkpoint inhibitor (ICI) treatment.

      • NOTE: Patients with well-controlled or clinically inactive autoimmune diseases are eligible
    • Non-infectious pneumonitis that required steroids, current pneumonitis, carcinomatous meningitis, or interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity

  • Known or ongoing illness or infection including:

    • Any active Grade 3 or higher [per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version (v) 5.0] viral, bacterial, or fungal infection ≤ 2 weeks of registration.

    • Acute hepatitis B (HBV) or acute hepatitis C virus (HCV)

      • NOTE: Patients with chronic HBV or HCV with adequate liver function per inclusion criteria are still eligible
    • Patients known to be HIV positive and currently receiving antiretroviral therapy
    • Known history of active tuberculosis (TB) (bacillus tuberculosis)
    • Uncontrolled hypertension and/or diabetes
    • Clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease requiring hospitalization ≤ 3 months prior to treatment)
  • Receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, radiotherapy, or any other investigational agent or therapy considered investigational (used for a non-Food and Drug Administration (FDA) approved indication and in the context of a research investigation)

  • Known concurrent malignancy that is progressing or requires active treatment

    • EXCEPTIONS: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in-situ cervical cancer that has been treated with curative intent, prostate cancer confined to the prostate gland with Gleason score ≤ 6, as well as any cancer treated with curative intent or any prior cancer with a disease-free interval of ≥ 3 years
  • History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (VSV-IFNβ-NIS, nivolumab, ipilimumab)

CYCLES 1-4: Patients receive nivolumab IV, over 30 minutes, and ipilimumab IV, over 30 minutes, on day 1 and VSV-IFNβ-NIS IV, over 30 minutes, on day 4 of cycle 1 only in the absence of disease progression or unacceptable toxicity. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

CYCLES 5+: Patients receive nivolumab IV, over 30 minutes, in the absence of disease progression or unacceptable toxicity. Cycles repeat every 28 days for a total of 2 years of treatment in the absence of disease progression or unacceptable toxicity.

Patients undergo CT scan and blood and urine sample collection throughout the study, as well as undergo tumor biopsy on study.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • CMAB819
  • Nivolumab Biosimilar CMAB819
  • MDX 1106
  • MDX1106
  • BMS 936558
  • ABP 206
  • Nivolumab Biosimilar ABP 206
  • BCD-263
  • Nivolumab Biosimilar BCD-263
  • BMS936558
  • ONO 4538
  • ONO4538
Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • Ipilimumab Biosimilar CS1002
  • MDX-010
  • MDX-CTLA4
  • Yervoy
  • MDX010
  • BMS734016
  • BMS 734016
  • MDX 010
Procedure: Computed Tomography
Undergo CT scan
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Procedure: Biospecimen Collection
Undergo blood and urine sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Biological: Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter
Given IV
Other Names:
  • Voyager-V1
  • Oncolytic VSV-hIFNbeta-NIS
  • Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter
  • VSV-expressing hIFNb and NIS
  • VSV-hIFNb-NIS
  • VSV-hIFNbeta-NIS
  • VV1
Procedure: Biopsy Procedure
Undergo tumor biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
  • Biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR)
Time Frame: Up to 5 years
A confirmed tumor response is defined to be a complete response (CR) or partial response (PR) noted as the objective status on two consecutive evaluations at least 4 weeks apart. Will be calculated overall and by cohort/subgroup using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Tumor response will be evaluated using all cycles of treatment.
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events (AEs)
Time Frame: Up to 90 days after end of treatment
The maximum grade for each type of AE will be recorded for each patient, graded according to NCI CTCAE v5.0.
Up to 90 days after end of treatment
Disease control rate (DCR)
Time Frame: Up to 5 years
Defined as the percentage of patients with a CR, PR or stable disease (SD) for at least 2 consecutive tumor assessments (i.e., confirmed CR/PR or SD for ≥ 12 weeks).
Up to 5 years
Duration of response (DOR)
Time Frame: Up to 5 years
Defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented.
Up to 5 years
Progression free survival (PFS)
Time Frame: Up to 5 years
Defined as the time from first dose of study drug to the earliest date of documented disease progression or death due to any cause. Assessed using RECIST 1.1.
Up to 5 years
Survival time
Time Frame: Up to 5 years
Defined as the time from first dose of study drug to death due to any cause. Assessed using RECIST 1.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Investigators

  • Principal Investigator: Brian A. Costello, MD, Mayo Clinic in Rochester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

August 1, 2033

Study Completion (Estimated)

August 1, 2033

Study Registration Dates

First Submitted

March 30, 2026

First Submitted That Met QC Criteria

March 30, 2026

First Posted (Actual)

April 3, 2026

Study Record Updates

Last Update Posted (Actual)

April 3, 2026

Last Update Submitted That Met QC Criteria

March 30, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MC250503
  • 25-008524 (Other Identifier: Mayo Clinic Institutional Review Board)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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