RP2 and Tivozanib for Metastatic Renal Cell Cancer
This study is testing a combination of two treatments, RP2 and tivozanib, for patients with metastatic renal cell cancer (kidney cancer that has spread) that has worsened after immunotherapy. RP2 is a modified herpes virus designed to infect and destroy cancer cells and activate your immune system. Tivozanib is a drug that may stop cancer cells from growing and prevent new blood vessels that tumors need. The study aims to see how many patients respond to this combination. You would need to be at least 18 years old and willing to provide a tumor biopsy. The study plans to enroll 35 participants.
- Study design
- This is a Phase II interventional study, meaning it tests new treatments in a group of people to see if they are effective and safe. It is designed to assess the overall response rate of the combination therapy.
- What's involved
- You would undergo tumor biopsies, blood and urine sample collection, and CT scans. RP2 is given directly into the tumor, and tivozanib is taken by mouth on specific days over several months.
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary outcome, objective response rate, is measured for up to 2 years.
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NCT07218692
RP2 and Tivozanib for the Treatment of Metastatic Renal Cell Cancer After Progression on Immunotherapy
Not Yet Recruiting
PHASE2Ages 18+InterventionalTreatmentCity of Hope Medical CenterInvestigator-initiated
~35 participants
Updated 2025-10-20 on ClinicalTrials.gov
What's tested:Biopsy ProcedureBiospecimen CollectionComputed TomographySturlimogene ErparepvecTivozanib
At a glance
Recruiting sites
0 of 2 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Objective response rate
Measured over Up to 2 years
Conditions
Where it's being run
2 sites across 1 statesCalifornia2
Study leadership
- Charles B Nguyen · PRINCIPAL_INVESTIGATOR · City of Hope Medical Center
Who to contact
Charles B. Nguyen
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Eligibility criteria
Inclusion
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
NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
Hemoglobin ≥ 9g/dL
NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment unless cytopenia is secondary to disease involvement
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless has Gilbert's disease)
Aspartate aminotransferase (AST) ≤ 3.0 x ULN
Alanine aminotransferase (ALT) ≤ 3.0 x ULN
Creatinine clearance of ≥ 30 mL/min per the Cockcroft-Gault formula or serum creatinine \< 1.5 x upper limit of normal (ULN)
If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN
If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
Left ventricular ejection fraction (LVEF) ≥ 50%
Note: To be performed within 28 days prior to day 1 of protocol therapy
QT interval corrected for heart rate using Bazetts's formula (QTcB) ≤ 480 ms
Note: To be performed within 28 days prior to day 1 of protocol therapy
Women of childbearing potential (WOCBP) must have a negative serum beta-human chorionic gonadotropin (β-hCG) test with a minimum sensitivity of 25 IU/L or equivalent units of β-hCG within 72 hours before the first dose and a negative urine pregnancy test on dose 1 day 1
Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at and for at least (a) 90 days after the last dose of RP2 or for one month after the last dose of tivozanib. Men must also agree to refrain from donating sperm during the treatment period and for at least 90 days after the last dose of RP2
Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
Exclusion
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)
Note 1: If HCV RNA testing not available, may use quantitative HCV RNA testing (preferred) or qualitative HCV antibody detection
Note 2: For patients with known acute or chronic hepatitis B virus (HBV) and/or HCV infection, HBV and/or HCV viral load by real-time polymerase chain reaction (qPCR) must be below the limit of quantitation for the laboratory test used, and they must not have had recent treatment within 12 weeks for HBV or HCV with antiviral medications. Patients with acute or chronic HBV or HCV must be expected to not require antiviral therapy during the RP2 treatment period
Clinically significant uncontrolled illness
Active significant herpetic infections or prior complications of herpes simplex virus 1 (HSV-1) infection (eg, herpetic keratitis or encephalitis) or requires intermittent or chronic use of systemic (oral or intravenous \[IV\]) antivirals with known antiherpetic activity (eg, acyclovir)
Note: Patients with sporadic cold sores may be enrolled if no active cold sores are present at the time of dose 1 day 1
Systemic infection requiring IV antibiotics or other serious infection within 14 days before dosing
Significant bleeding event within the last 12 months that places the patient at unjustifiable risk for bleeding from intratumoral injection procedures, based on Investigator or interventional radiologist assessment
Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Known central nervous system (CNS) metastases and/or carcinomatous meningitis
History of interstitial lung disease, idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), non-infectious pneumonitis that required steroids, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
Note: History of radiation pneumonitis in the radiation field (fibrosis) is permitted
Active tuberculosis
History or evidence of psychiatric, substance abuse, or any other clinically significant disorder, condition, or disease (except for those outlined above) that, in the opinion of the investigator or the medical monitor, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion
Active, known, or suspected autoimmune disease requiring systemic treatment
Note: Patients with type 1 diabetes mellitus and/or hypothyroidism requiring only hormone replacement, and/or with autoimmune skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, and/or prior non-serious autoimmune conditions not expected to recur are permitted to enroll
Conditions requiring treatment with immunosuppressive doses (\> 10 mg per day of prednisone or equivalent) of systemic corticosteroids within 14 days before dose 1 day 1
Note: Patients who require a brief course (≤ 7 days) of corticosteroids (eg, as prophylaxis for imaging studies due to hypersensitivity to contrast agents) are not excluded. Physiologic replacement doses of systemic corticosteroids are permitted, only if the dose does not exceed 10 mg/day prednisone equivalent
History of life-threatening toxicity related to prior immune therapy (eg, anti-cytotoxic T lymphocyte antigen 4 or anti-PD-1/anti-PD-L1 treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways \[eg, CD40,4-1BB\]) except those that are unlikely to recur or are expected to be manageable with standard countermeasures (eg, hormone replacement after adrenal crisis). Individual cases should be discussed with medical monitor if needed
Conditions in which anticoagulant therapies cannot be safely stopped in the periprocedural period or patients on coumadin with a target INR \> 2.5 or that cannot be temporarily reversed to INR ≤ 1.7
Treatment with botanical preparations (eg, herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks before treatment
Prior organ transplantation including allogeneic stem-cell transplantation
Major surgery within 28 days before starting treatment or anticipated major surgery while on study
Note: If a patient received major surgery, they must have recovered adequately from the intervention before starting study treatment and must have adequate wound healing, based on investigator's assessment or surgeon's assessment, before starting tivozanib
Females only: Pregnant or breastfeeding
History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
What this trial measures
- Objective response rateUp to 2 years
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.