Zanzalintinib for Metastatic Clear Cell Renal Cell Carcinoma With Bone Metastases

Recruiting now · Phase 2

Conditions studied: Clear Cell Renal Cell Cancer (ccRCC), Clear Cell Renal Carcinoma, Clear Cell Renal Cell Carcinoma Metastatic, Clear Cell Renal Cancer, Bone Metastases of a Malignant Tumor, Clear Cell Renal Cell Carcinoma, Bone, Metastatic Cancer, Metastatic Cancer, Metastatic Renal Cell Carcinoma, Metastases to Bone

In brief

This is a single-institution, phase 2 trial of zanzalintinib plus investigator-choice bone-strengthening agent in patients with metastatic renal cell carcinoma (RCC) with bone metastases whose disease has advanced on 1-3 prior lines of therapy, including at least one immune oncology-based (IO) therapy in the adjuvant or first-line metastatic setting.

Key facts

Study ID

NCT07043608

Run by

Kelly Fitzgerald, MD

People needed

20

Starts

2026-06-10

Expected to finish

2030-04-30

Last updated by the study team

2026-07-27

Who can join

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

You may qualify if…

• Participants must have unresectable advanced or metastatic RCC with a predominant clear cell histologic component .
• At least three bone metastases are present and detectable on bone scan, and at least one bone metastasis is NOT planned to be treated with radiation therapy.
• Previously treated with 1-3 prior lines of therapy in at least one of the following settings:
• Metastatic setting; must have received combination therapy containing either programmed cell death protein 1 (PD-1) inhibitor/cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor or PD-1 inhibitor/vascular endothelial growth factor receptor (VEGFR)-targeting tyrosine kinase inhibitors (TKI).
• Adjuvant setting; must have received pembrolizumab and have had documented progression of disease within 1 year of the first dose of pembrolizumab .
• Age ≥18 years.
• Has seen a dentist within 90 days prior to enrollment and been cleared to receive bone-strengthening agents.
• Availability of a representative formalin fixed, paraffin embedded tumor specimen or fresh frozen tissue specimen that enables the definitive diagnosis of RCC, accompanied by an associated pathology report. If stored specimens are not available, an optional biopsy may be performed and specimens can be collected by surgical resection or biopsy of the primary tumor or biopsy or resection of a metastatic lesion.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Demonstrates adequate organ function as defined below within 14 days prior to first study treatment:
• Absolute neutrophil count (ANC) >=1,500/ μL (without granulocyte colony stimulating factor support within 2 weeks prior to Cycle 1, Day 1).
• Platelets ≥100,000/ μL (without transfusion within 2 weeks prior to Cycle 1, Day 1).
• White Blood Cell count (WBC) counts ≥ 2500/μL.
• Lymphocyte count ≥ 500/μL.
• Hemoglobin ≥9.0 g/dL.
• Participants may be transfused or receive erythropoietic treatment to meet this criterion:
• Serum bilirubin ≤ 1.5 x upper limit of normal (ULN). Participants with known Gilbert disease who have serum bilirubin level <= 3 x ULN may be enrolled.
• Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) ≤2.5 X institutional upper limit of normal.
• Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤2.5 X institutional upper limit of normal.
• Alkaline phosphatase ≤2.5 X institutional upper limit of normal. For participants with documented liver metastases: AST and/or ALT ≤ 5 x ULN. For participants with documented liver or bone metastases: alkaline phosphatase ≤ 5 x ULN.
• Creatinine ≤ 1.5 x within institutional upper limit of normal OR creatinine clearance ≥ 40 mL/min by institutional standard AND urine protein-creatinine ratio (UPCR) 1mg/mg.
• International Normalized Ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN. This applies only to participants who are not receiving therapeutic anticoagulation; participants receiving therapeutic anticoagulation should be on a stable dose.
• Serum ionized calcium above lower limit of normal and ≤ 1.5 x ULN.
• If any Grade ≥1 toxicities occurred in relation to prior treatment, patients must have recovered to baseline or ≤ Grade 1 unless adverse events are clinically insignificant or stable on supportive medication if needed.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if…

• Prior treatment with zanzalintinib for RCC.
• Receipt of any small molecule kinase inhibitor (including investigational) or vascular endothelial growth factor (VEGF)-targeted therapy within 2 weeks before the first dose of study treatment.
• 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.
• Participants requiring whole brain radiotherapy (WBRT).
• Incomplete healing from prior radiotherapy as determined by the treating radiation oncologist or treating investigator.
• Participation in an experimental drug study within 28 days of study enrollment.
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
• Pregnant and lactating women are excluded from this study because zanzalintinib is an investigational product with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with zanzalintinib, breastfeeding should be discontinued if the mother is treated with zanzalintinib.
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Cycle 1, Day 1.
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation); Clinically significant hematuria, hematemesis, or hemoptysis of >0.5 tsp (2.5ml) of red blood or other history of significant bleeding within 12 weeks before first dose of study treatment.
• Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding.
• Evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
• Concomitant anticoagulation with coumarin agents, direct thrombin inhibitors, factor Xa inhibitor betrixaban, or platelet inhibitors. Other anticoagulants are allowed.
• 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.
• i. Participants who have known brain metastases and who require therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban are not eligible for this study.
• ii. Participants with known brain metastases and who are taking prophylactic low-dose aspirin for cardioprotection or low-dose (prophylactic-dose) low molecular weight heparin are eligible.
• Note: Subjects must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first dose of study treatment, whichever is longer.
• Previously identified allergy or hypersensitivity to components of the treatment.
• Malignancy that requires anti-cancer directed therapy within the last 3 years. Exceptions include those cancers that are considered cured by local therapy (e.g. Basal cell carcinoma, squamous cell carcinoma, ductal carcinoma in situ of breast, bladder, or cervix) or other cancers that have low malignant potential and do not require systemic therapy (e.g. Gleason grade <6 prostate adenocarcinoma).
• 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.
• 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:

Where it is running

• University of California, San Francisco — San Francisco, California, United States (enrolling)

Full record on ClinicalTrials.gov

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