Zanzalintinib and MO-03 for the Treatment of Metastatic Renal Cell Cancer After Progression on Immunotherapy

Starting soon · Phase 2

Conditions studied: Metastatic Clear Cell Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8

In brief

This phase II trial tests how well zanzalintinib and MO-03 works for the treatment of 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 (progression) after receiving immunotherapy. Zanzalintinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. MO-03 is a type of medication called a microbiome-based immunomodulator. It helps control some of the bacteria found in the gut which may make the zanzalintinib more effective. Giving zanzalintinib with MO-03 may be effective for treating metastatic renal cell cancer after progression on immunotherapy.

Key facts

Study ID

NCT07578025

Run by

City of Hope Medical Center

People needed

34

Starts

2026-11-28

Expected to finish

2028-06-24

Last updated by the study team

2026-05-11

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Capable of understanding and complying with the protocol requirements and must have signed the informed consent document
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: ≥ 18 years
• Gender: Males and females are eligible
• Any ethnicity or race
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Histologically confirmed renal cell carcinoma with a clear-cell histology
• Patients must have received one or two prior lines of systemic therapy for metastatic disease, which must include prior treatment with a checkpoint inhibitor and cabozantinib (not necessarily in the same line). Prior use of hypoxia-inducible factor (HIF) inhibitors or other tyrosine kinase inhibitors (TKIs) other than cabozantinib are not allowed
• Measurable metastatic disease by RECIST v 1.1 criteria
• Recovery to baseline or ≤ grade 1 severity (CTCAE v 6.0) from adverse events (AEs), including immune-related adverse events (irAEs), related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy (e.g., physiological replacement of corticosteroid). Low-grade or controlled toxicities such as alopecia, ≤ grade 2 hypomagnesemia, ≤ grade 2 neuropathy are permitted)
• White blood cell (WBC) > 2,000/mm\^3 (to be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• NOTE: Growth factor is not permitted within 14 days of absolute neutrophil count (ANC) assessment unless cytopenia is secondary to disease involvement
• Neutrophils ≥ 1,500/mm\^3 (to be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• NOTE: Growth factor is not permitted within 14 days of absolute neutrophil count (ANC) assessment unless cytopenia is secondary to disease involvement
• Platelets ≥ 100,000/mm\^3 (to be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
• Hemoglobin ≥ 9g/dL (to be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• 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) (except for subjects with Gilbert Syndrome, who may have total bilirubin up to 3.0 mg/dL) (to be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• Aspartate aminotransferase (AST) ≤ 3.0 x ULN (except for subjects with Gilbert Syndrome, who may have total bilirubin up to 3.0 mg/dL) (to be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• Alkaline phosphatase (ALP) ≤ 3.0 x ULN. For subjects with documented bone metastasis ALP ≤ 5 x ULN (to be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• Creatinine clearance ≥ 40 mL/min the Cockcroft-Gault formula (to be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• 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 (to be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.2 x ULN, INR ≤ 1.5. If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants (to be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)

You may not qualify if…

• Prior treatment with zanzalintinib
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment
• Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment
• Note: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment.
• Note: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed
• Known medical condition (e.g., chronic diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results
• Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin inhibitors ) and platelet inhibitors (e.g., clopidogrel).Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen.
• Note: Subjects must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first dose of study treatment, whichever is longer
• Any complementary medications (e.g., herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Unstable or deteriorating cardiovascular disorders:
• Congestive heart failure New York Heart Association Class 3 or 4, class 2 or higher, unstable angina pectoris, new-onset angina, serious cardiac arrhythmias (e.g., ventricular flutter, ventricular fibrillation, Torsades de pointes).
• Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
• Stroke (including transient ischemic attack [TIA]), myocardial infarction, or other clinically significant arterial thrombotic and/or ischemic event within 6 months before first dose of study treatment.
• Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous events within 3 months before first dose of study treatment.
• Note: Subjects with a diagnosis of DVT within 6 months are allowed if asymptomatic and stable at screening and are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen.
• Note: Subjects who don't require prior anticoagulation therapy may be eligible but must be discussed and approved by the Principal Investigator
• Prior history of myocarditis.
• Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
• Tumors invading the GI-tract from external viscera.
• Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis.
• Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months before first dose unless cause of obstruction is definitively managed and subject is asymptomatic.

Where it is running

• City of Hope Medical Center — Duarte, California, United States

Full record on ClinicalTrials.gov

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