Recruiting

Phase 2

IvonescimabIvonescimab Prior to Surgery for the Treatment of High-Risk Localized Clear Cell Renal Cell Cancer

Sponsor:

City of Hope Medical Center

Code:

NCT07226544

Conditions

Localized Clear Cell Renal Cell Carcinoma

Resectable Clear Cell Renal Cell Carcinoma

Stage II Renal Cell Cancer AJCC v8

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

Echocardiography Test

Ivonescimab

Study Details

Brief summary:

This phase II trial studies how well ivonescimab works prior to surgery in treating patients with high-risk clear cell kidney (renal cell) cancer that has not spread to other parts of the body (localized). Immunotherapy with monoclonal antibodies, such as ivonescimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ivonescimab may also stop or slow the cancer by blocking the growth of new blood vessels necessary for tumor growth. Giving ivonescimab before standard surgery may make the tumor smaller.

Conditions

Localized Clear Cell Renal Cell Carcinoma

Resectable Clear Cell Renal Cell Carcinoma

Stage II Renal Cell Cancer AJCC v8

Stage III Renal Cell Cancer AJCC v8

Stage IV Renal Cell Cancer AJCC v8

Study ID

NCT07226544

Start date

Oct 1, 2026

Status verified date

Aug, 2026

Completion date

Sep 8, 2027

Anticipated

Primary completion date

Sep 8, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Histologic confirmation of clear cell RCC
High-risk disease defined as cT2G3-4N0M0, cT3GanyN0M0, cT4GanyN0M0, cTanyGanyN+M0 (Grade determined by biopsy)
Candidate for partial or complete nephrectomy that extirpates all tumor tissue as part of treatment plan
Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L (no blood transfusions or growth factor therapy used within 7 days of the screening complete blood count \[CBC\])
Platelet count ≥ 100 × 10\^9/L (no blood transfusions or growth factor therapy used within 7 days of the screening CBC)
Hemoglobin ≥ 9.0 g/dL (no blood transfusions or growth factor therapy used within 7 days of the screening CBC)
Creatinine clearance (CrCL) ≥ 50 mL/min using the Cockcroft-Gault formula or estimated glomerular filtration rate (eGFR) value ≥ 60 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (adjustment by body surface area \[BSA\] is not required for eGFR)
Urine protein < 2+ or 24-hour urine protein quantification < 1.0 g
Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); For patients with liver metastases or confirmed/suspected Gilbert syndrome, TBIL ≤ 3 × ULN
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; For patients with liver metastases, AST and ALT ≤ 5 × ULN
Coagulation: Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 × ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy). This applies only to patients who are not on therapeutic anti-coagulation. Patients receiving therapeutic anti-coagulation should be on a stable dose
Female patients of childbearing age must have negative serum pregnancy test results before enrollment or per region-specific guidance documented in the informed consent and a negative urine pregnancy test on the day of first dose prior to dosing
Female patient of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 90 days after the last dose of the ivonescimab
Unsterilized male patients having sex with a female partner of childbearing potential, or a pregnant or breastfeeding partner must agree to use barrier contraception (male condom) for the duration of the treatment period until 90 days after the last dose of ivonescimab. Male patients with female partners of childbearing potential must have the female partner agree to use at least 1 form of highly effective contraception for the duration of the treatment period until 90 days after the last dose of ivonescimab
Adults aged 18 years or older

Exclusion Criteria:

Prior systemic anti-tumor treatment for RCC
Major surgical procedures or serious trauma within 4 weeks prior to enrollment, or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to enrollment
History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to enrollment, including but not limited to:

Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to enrollment is not allowed. The use of full-dose anticoagulants is permitted as long as the international normalized ratio (INR) or activated partial thromboplastin time (aPTT) is within therapeutic limits according to the medical standard of the enrolling institution
Poorly controlled hypertension with repeated systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy
Active autoimmune or lung disease requiring systemic therapy (eg, with disease modifying drugs, prednisone > 10 mg daily or equivalent, immunosuppressant therapy) within 2 years prior to enrollment, however the following will be allowed:

Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted
Intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections is permitted
History of major diseases before enrollment, specifically:

Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade 2) or unstable vascular disease (eg, aortic aneurysm at risk of rupture, Moyamoya disease) that required hospitalization within 12 months prior to enrollment, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia)
History of esophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months before enrollment
History of any grade arterial thromboembolic event, Grade 3 and above venous thromboembolic event, as specified in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 12 months prior to enrollment
Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before enrollment
History of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months prior to enrollment
Imaging during the screening period shows that the patient has metastatic disease
Symptomatic central nervous system (CNS) metastases, CNS metastases with hemorrhagic features, CNS metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to enrolment, potential need for CNS radiation within the first cycle, or leptomeningeal disease
Live vaccine or live attenuated vaccine within 4 weeks prior to planned enrolment, or if scheduled to receive a live vaccine or live attenuated vaccine during the study period. Inactivated vaccines are permitted
Severe infection within 4 weeks prior to enrolment, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; active infection (as determined by the investigator) requiring systemic anti-infective therapy within 2 weeks prior to enrolment (excluding antiviral therapy for hepatitis B or C)
Has pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE version 5
Uncontrolled pleural effusions, pericardial effusions, or ascites that is clinically symptomatic
History of non-infectious pneumonia requiring systemic corticosteroids, or current interstitial lung disease
Active or prior history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
Known history of human immunodeficiency virus (HIV) whose viral load is not controlled
Current use of systemic corticosteroids (> 10 mg daily prednisone or equivalent)
Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation
Patients with active hepatitis B are required to have stable or declining levels of hepatitis B DNA by polymerase chain reaction (PCR) on appropriate anti-viral therapy with acceptable tolerability for one month prior to enrolment. All patients with active hepatitis C (hepatitis C virus \[HCV\] antibody positive with HCV ribonucleic acid \[RNA\] levels above the lower limit of detection) are excluded
Known allergy to any component of any study drug; known history of severe hypersensitivity to other monoclonal antibodies
History or current evidence of any condition (medical \[including adverse events from prior anticancer therapy, disorders secondary to tumor\], surgical or psychiatric \[including substance abuse\]), or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, might lead to higher medical risk and/or is not in the best interest of the patient to participate, in the opinion of the treating investigator
Patient is breastfeeding or plans to breastfeed during the study
History of severe immune-mediated adverse events from immunotherapy agents (i.e. PD1/PDL1/CTLA4 inhibitors), or immune-related ocular toxicity, pneumonitis, or cardiomyopathy of any grade

Study Design

Enrollment

31 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (ivonescimab)

Patients receive ivonescimab IV over 60-120 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Between 4-10 weeks after completion of ivonescimab treatment, patients then undergo SOC nephrectomy. Patients also undergo ECHO during screening, biopsy prior to treatment start, and CT and blood sample collection throughout the study.

Interventions

Biopsy Procedure

Undergo biopsy

Biospecimen Collection

Undergo blood sample collection

Computed Tomography

Undergo CT

Echocardiography Test

Undergo ECHO

Ivonescimab

Given IV

Nephrectomy

Undergo SOC nephrectomy

Questionnaire Administration

Ancillary studies

Primary outcome measure

Proportion of patients achieving a best overall response (ORR) [ Time Frame: Up to 2 years after completion of study treatment ]

Central Contacts and Locations

Locations

City of Hope Medical Center

Recruiting

Duarte, California, United States, 91010

Contacts

Wesley Yip

626-218-3396 wyip@coh.org

Principal Investigator:

Wesley Yip

More Information

Sponsor

City of Hope Medical Center

Last update posted

Aug 5, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by City of Hope Medical Center on 2026-08-05.