Recruiting

Phase 2

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

Sponsor:

Mayo Clinic

Code:

NCT07510334

Conditions

Advanced Clear Cell Renal Cell Carcinoma

Metastatic Clear Cell Renal Cell Carcinoma

Stage III Renal Cell Cancer AJCC v8

Stage IV Renal Cell Cancer AJCC v8

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biopsy Procedure

Biospecimen Collection

Computed Tomography

Ipilimumab

Nivolumab

Study Details

Brief summary:

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.

Conditions

Advanced Clear Cell Renal Cell Carcinoma

Metastatic Clear Cell Renal Cell Carcinoma

Stage III Renal Cell Cancer AJCC v8

Stage IV Renal Cell Cancer AJCC v8

Study ID

NCT07510334

Start date

Apr 21, 2026

Status verified date

Jun, 2026

Completion date

Aug 1, 2033

Anticipated

Primary completion date

Aug 1, 2033

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

18 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

Interventions

Biopsy Procedure

Undergo tumor biopsy

Biospecimen Collection

Undergo blood and urine sample collection

Computed Tomography

Undergo CT scan

Ipilimumab

Given IV

Nivolumab

Given IV

Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter

Given IV

Primary outcome measure

Objective response rate (ORR) [ Time Frame: Up to 5 years ]

Central Contacts and Locations

Central contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Locations

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Principal Investigator:

Brian A. Costello, MD

More Information

Sponsor

Mayo Clinic

Last update posted

Jun 5, 2026

Last verified

Jun, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Mayo Clinic on 2026-06-05.