RP2 and Tivozanib for the Treatment of Metastatic Renal Cell Cancer After Progression on Immunotherapy

NCT07218692 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 25317NCI-2025-07332P30CA033572
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial tests the effect of RP2 and tivozanib in treating patients with renal cell cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and that is growing, spreading, or getting worse (progressive) after receiving immunotherapy with immune checkpoint inhibitors (ICIs). RP2 is a herpes simplex virus (a viral infection commonly known as the "cold sore virus") that has been changed to infect and destroy tumor cells and to activate (turn on) the human immune system to attack the tumor cells. Tivozanib hydrochloride blocks certain proteins, which may help keep tumor cells from growing. It may also prevent the growth of new blood vessels that tumors need to grow. Tivozanib hydrochloride is a type of tyrosine kinase inhibitor and a type of antiangiogenesis agent. Giving RP2 and tivozanib may be safe, tolerable, and/or effective in treating patients with metastatic renal cell cancer that has progressed after receiving immunotherapy with ICIs.

Conditions

Advanced Clear Cell Renal Cell Carcinoma; Advanced Renal Cell Carcinoma; Advanced Sarcomatoid Renal Cell Carcinoma; Metastatic Clear Cell Renal Cell Carcinoma; Metastatic Renal Cell Carcinoma; Metastatic Sarcomatoid Renal Cell Carcinoma; Recurrent 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

  Will be defined as the proportion of patients who achieve a complete response (CR) or partial response (PR) per the Response Evaluation Criteria in Solid Tumors version (v) 1.1. Will be calculated as the number of patients with CR or PR divided by the total number of treated and evaluable subjects. Will be summarized with 80% confidence intervals.

  Up to 2 years

Secondary Outcomes (4)

• Progression-free survival (PFS)

  From start of treatment to progression or death, whichever occurs first, assessed up to 2 years

• Overall survival (OS)

  From start of treatment to death from any cause, assessed up to 2 years

• Incidence of adverse events (AEs)

  Up to 30 days after last dose of study treatment

• Baseline characteristics

  At baseline

Study Arms (1)

Treatment (RP2, tivozanib)

EXPERIMENTAL

Patients receive RP2 intratumorally on days 1, 15, 29, 43, 64, 85, 106, and 127. Treatment repeats every 2 weeks for the first 4 doses and then every 3 weeks for subsequent doses for up to 8 doses in the absence of disease progression or unacceptable toxicity. After completion of the first course of treatment, patients who meet criteria may receive another course of RP2 intratumorally every 3 weeks for up to an additional 8 doses. Patients also receive tivozanib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT and urine and blood sample collection throughout the study. Additionally, patients may undergo tumor biopsies throughout the study.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Sturlimogene Erparepvec; Drug: Tivozanib

Interventions

Biospecimen Collection PROCEDURE

Undergo urine and blood sample collection

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

Treatment (RP2, tivozanib)

Biopsy Procedure PROCEDURE

Undergo tumor biopsies

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (RP2, tivozanib)

Computed Tomography PROCEDURE

Undergo CT

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 (RP2, tivozanib)

Sturlimogene Erparepvec BIOLOGICAL

Given intratumorally

Also known as: Oncolytic Herpes Simplex Virus-1 Expressing Anti-CTLA-4 Antibody-like Molecule and GM-CSF RP2, Oncolytic Herpes Simplex Virus-1 Expressing Anti-CTLA-4 Antibody-like Molecule/GM-CSF RP2, Oncolytic HSV-1 Expressing Anti-CTLA-4 Antibody-like Molecule and GM-CSF RP2, Oncolytic HSV-1 Expressing Anti-CTLA-4 Antibody-like Molecule/GM-CSF RP2, Oncolytic Virus RP2, RP 2, RP-2, RP2

Treatment (RP2, tivozanib)

Tivozanib DRUG

Given PO

Also known as: AV 951, AV-951, AV951

Treatment (RP2, tivozanib)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Must be willing to consent to provide fresh tumor biopsy sample or archival tumor biopsy sample obtained within 90 days before the first dose of study treatment
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Male or female who is 18 years of age or older at the time of signed informed consent
• Eastern Cooperative Oncology Group (ECOG) 0 or 1
• Histologically confirmed renal cell carcinoma with a clear-cell or sarcomatoid component
• Patients must have received exactly one prior line or two prior lines of systemic therapy in the advanced or metastatic setting, including mandatory exposure to both an immune checkpoint inhibitor (ICI) and one antiangiogenic tyrosine kinase inhibitor (TKI). Prior treatment with hypoxia inducible factor (HIF)-α inhibitors is not permitted. Patients who received adjuvant immunotherapy and experienced disease recurrence within 6 months of completing treatment may also be eligible, and such therapy will count toward prior lines
• Has injectable tumor(s), which alone or in aggregate, total at least 1 cm in diameter of RP2
• Has at least 1 measurable tumor of ≥ 1 cm in longest diameter (or ≥ 1.5 cm shortest diameter for lymph nodes) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
• White blood cell (WBC) count ≥ 2.0 x 10\^9/L
• Absolute neutrophil count (ANC) ≥ 1,500/mm\^3
• NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement
• Platelets ≥ 100,000/mm\^3

You may not qualify if:

• Received a live vaccine within 28 days before the first dose of study treatment
• Note: Seasonal influenza vaccines for injection or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are generally inactivated vaccines and are allowed. Live/attenuated vaccines (such as the intranasal influenza vaccines) are not allowed
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study treatment
• Note: Patients who have entered the follow-up phase of an investigational study may participate if it has been 4 weeks after the last dose of the previous investigational agent
• Systemic anticancer therapies within 4 weeks of the first dose of study drug. The prior anti-PD-1 or anti-PD-L1 containing regimen is excluded from this requirement
• Received prior treatment with an oncolytic virus therapy
• Received radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities (except for radiation-induced xerostomia), not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-central nervous system (CNS) disease
• Note: Patients must have recovered (to grade ≤ 1 or baseline) from all adverse events (AEs) due to previous therapies. Patients with grade ≤ 2 neuropathy may be eligible if approved by the medical monitor
• Unstable cardiac disease as defined by one of the following:
• Cardiac events such as myocardial infarction (MI) within the past 6 months
• NYHA (New York Heart Association) heart failure class III-IV
• Uncontrolled atrial fibrillation or hypertension
• History of allergy or sensitivity to study drug components or prior monoclonal antibody treatment; known hypersensitivity to Chinese hamster ovary cell products
• Known human immunodeficiency virus (HIV) infection
• Known acute or chronic hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known acute or chronic hepatitis C virus (defined as HCV ribonucleic acid \[RNA\] \[qualitative\] is detected)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

Location

MeSH Terms

Conditions

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

Interventions

Biopsy; Specimen Handling; tivozanib

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

Study Officials

• Charles B Nguyen

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

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: October 16, 2025
• First Posted: October 20, 2025
• Study Start (Estimated): August 11, 2026
• Primary Completion (Estimated): August 11, 2027
• Study Completion (Estimated): August 11, 2027
• Last Updated: October 20, 2025

Record last verified: 2025-10

Locations

US (2)