Phase II Trial of Ivonescimab in Previously Treated Patients With Advanced Clear Cell Renal Cell Carcinoma

NCT06940518 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2025-0277NCI-2025-02811
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if ivonescimab can help to control previously treated, locally advanced or metastatic ccRCC.

Conditions

Ivonescimab; Clear Cell Renal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version

  Through study completion; an average of 1 year.

Study Arms (2)

Cohort 2 - (Post-ICB/VEGFTKI)

EXPERIMENTAL

Treatment with Ivonescimab IV Q3W

Drug: Ivonescimab

Cohort 1 - (Post-pure-ICB)

EXPERIMENTAL

Treatment with Ivonescimab IV Q3W

Drug: Ivonescimab

Interventions

Ivonescimab DRUG

Given by IV

Cohort 1 - (Post-pure-ICB); Cohort 2 - (Post-ICB/VEGFTKI)

Eligibility Criteria

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

You may qualify if:

• Participants with histologically or cytologically confirmed metastatic/advanced clear cell RCC with a clear cell component who have received at least one prior line of systemic treatment in the advanced or metastatic setting, including a PD-1/PD-L1 checkpoint inhibitor administered in metastatic/advanced setting.
• Participants in cohort 1 must have not received a treatment containing a VEGF- or HIF2a(- directed agent in prior treatment lines of treatment for metastatic/advanced RCC
• Participants in cohort 2 must have had progression on or after at least one prior line of treatment containing a VEGF-directed agent in prior lines of therapy
• Participants must have had evidence of disease progression on or after last treatment regimen received.
• Participants who received HIF-2ƒ¿ inhibitors in prior lines of therapy are eligible in cohort 2 but not cohort 1.
• Participants who received adjuvant immune checkpoint inhibitor are eligible, provided that they had progression while on adjuvant therapy, in which case they would be enrolled in cohort 1. Participants who recur after completing adjuvant therapy should receive a PD-1/PD-L1 checkpoint inhibitor in the advanced/metastatic setting to be eligible.
• Participants must have at least one measurable site of disease per RECIST version 1.1. This is defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). For non-lymph node tumor lesions, they must be a minimum size of ≥ 10 mm. For malignant lymph node lesions, they must be at least ≥ 15 mm in short axis with conventional techniques or ≥10 mm with more sensitive techniques such as MRI or spiral CT scan. If the participant has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
• ECOG performance status ≤2
• Age ≥ 18 years
• Participants must have adequate organ and marrow function prior to study entry as defined below:
• INR and PT ≤ 1.5 x ULN and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤1.5 ULN (unless abnormalities are unrelated to coagulopathy). Therapeutic anticoagulation is permitted if: on a stable dose of low molecular weight heparin (LMWH) for \> 2 weeks (14 days) at the time of enrollment or on a direct oral anticoagulant (DOAC) for \> 2 weeks at time of enrollment.
• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Patients who are Hepatitis C virus antibody positive (HCV Ab
• +) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.

You may not qualify if:

• Participants must not have any other malignancies within the past 2 years except for in situ carcinoma of any site, or adequately treated (without recurrence post-resection or postradiotherapy) carcinoma of the cervix or basal or squamous cell carcinomas of the skin, ductal carcinoma in situ of the breast or low-risk early stage prostate adenocarcinoma with negligible risk of metastasis or death.
• 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.
• Current hypertension with systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg after adequate oral antihypertensive therapy.
• 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:
• o Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots).
• Transient hemoptysis associated with diagnostic bronchoscopy is allowed.
• Nasal bleeding /epistaxis. Bloody nasal discharge is allowed.
• Hematuria associated with urinary obstruction. Microhematuria or macrohematuria not associated with urinary obstruction are allowed.
• Radiologically documented evidence of major blood vessel encasement with narrowing of the vessel that the investigator determines will pose a significantly increased risk of bleeding.
• History of major diseases prior to enrollment, specifically:
• Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \[NYHA\] classification . grade 2) or vascular disease (eg, aortic aneurysm at risk of rupture) that required hospitalization within 12 months prior to randomization, 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 prior to enrollment.
• History of arterial thromboembolic event, venous thromboembolic event of Grade 3 and above 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 prior to 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Strategic Alliance: collaborator
• Summit Therapeutics: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Carcinoma, Renal Cell

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

Study Officials

• Pavlos Msaouel, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pavlos Msaouel, MD

CONTACT

713-563-4585; pmsaouel@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: April 15, 2025
• First Posted: April 23, 2025
• Study Start: July 2, 2025
• Primary Completion (Estimated): January 19, 2028
• Study Completion (Estimated): January 19, 2030
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (1)