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

NCT07510334 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: MC25050325-008524
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  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 Outcomes (5)

• Incidence of adverse events (AEs)

  Up to 90 days after end of treatment

• Disease control rate (DCR)

  Up to 5 years

• Duration of response (DOR)

  Up to 5 years

• Progression free survival (PFS)

  Up to 5 years

• Survival time

  Up to 5 years

Study Arms (1)

Treatment (VSV-IFNβ-NIS, nivolumab, ipilimumab)

EXPERIMENTAL

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.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Ipilimumab; Biological: Nivolumab; Biological: Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter

Interventions

Biopsy Procedure PROCEDURE

Undergo tumor biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (VSV-IFNβ-NIS, nivolumab, ipilimumab)

Biospecimen Collection PROCEDURE

Undergo blood and urine sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (VSV-IFNβ-NIS, nivolumab, ipilimumab)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (VSV-IFNβ-NIS, nivolumab, ipilimumab)

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016, Ipilimumab Biosimilar CS1002, MDX 010, MDX-010, MDX-CTLA4, MDX010, Yervoy

Treatment (VSV-IFNβ-NIS, nivolumab, ipilimumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo

Treatment (VSV-IFNβ-NIS, nivolumab, ipilimumab)

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

Given IV

Also known as: Oncolytic VSV-hIFNbeta-NIS, Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter, Voyager-V1, VSV-expressing hIFNb and NIS, VSV-hIFNb-NIS, VSV-hIFNbeta-NIS, VV1

Treatment (VSV-IFNβ-NIS, nivolumab, ipilimumab)

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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Clear-cell metastatic renal cell carcinoma; Carcinoma, Renal Cell

Interventions

Biopsy; Specimen Handling; Ipilimumab; CTLA-4 Antigen; Nivolumab; sodium-iodide symporter

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Study Officials

• Brian A. Costello, MD

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.edu

Study Design

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

Study Record Dates

• First Submitted: March 30, 2026
• First Posted: April 3, 2026
• Study Start: April 21, 2026
• Primary Completion (Estimated): August 1, 2033
• Study Completion (Estimated): August 1, 2033
• Last Updated: June 5, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)