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

NCT07226544 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 25395NCI-2025-07733P30CA033572
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Proportion of patients achieving a best overall response (ORR)

  Objective response is defined as complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors. The ORR will be estimated as the proportion of patients who have CR or PR during the treatment, along with the 90% and 95% exact confidence intervals.

  Up to 2 years after completion of study treatment

Secondary Outcomes (6)

• Incidence of adverse events (AEs)

  Up to 30 days after completion of study treatment

• Rate of completion of surgery

  At least 4 weeks after and within 10 weeks of the last cycle of ivonescimab (each cycle is 21 days)

• Pathologic complete response (pCR)

  Up to 2 years after completion of study treatment

• Peri-treatment KIM-1 levels

  Prior to surgery and after completion of Cycle 4 (each cycle is 21 days)

• Recurrence-free survival

  From date of surgery to disease recurrence or death from any cause, whichever occurs first, assessed up to 2 years after completion of study treatment

Study Arms (1)

Treatment (ivonescimab)

EXPERIMENTAL

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.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Biological: Ivonescimab; Procedure: Nephrectomy; Other: Questionnaire Administration

Interventions

Nephrectomy PROCEDURE

Undergo SOC nephrectomy

Treatment (ivonescimab)

Questionnaire Administration OTHER

Ancillary studies

Treatment (ivonescimab)

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (ivonescimab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Treatment (ivonescimab)

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 (ivonescimab)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (ivonescimab)

Ivonescimab BIOLOGICAL

Given IV

Also known as: AK 112, AK-112, AK112, Anti-PD-1/Anti-VEGF Bispecific Antibody AK112, Anti-PD-1/VEGF Bispecific Antibody AK112, PD-1/VEGF Bispecific Antibody AK112, SMT 112, SMT-112, SMT112

Treatment (ivonescimab)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Biopsy; Specimen Handling; Nephrectomy

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; Urologic Surgical Procedures; Urogenital Surgical Procedures

Study Officials

• Wesley Yip

  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: November 5, 2025
• First Posted: November 10, 2025
• Study Start: June 8, 2026
• Primary Completion (Estimated): September 8, 2027
• Study Completion (Estimated): September 8, 2027
• Last Updated: June 10, 2026

Record last verified: 2026-06

Locations

US (1)