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.
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.
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 .
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).
Single group
Zanzalintinib
DrugGiven orally (PO)
Investigator Choice of Bone Strengthening Agents (BSA)
DrugOne BSA will be chosen, at the discretion of the investigator and given intravenously (IV)
Non-Investigational Radiation Therapy (RT)
RadiationNon-investigational RT is permitted for symptomatic bone metastases.
Bone Scan
Procedure/SurgeryUndergo Bone Scan
Computerized tomography (CT) Scan
Procedure/SurgeryUndergo Imaging
Proportion of participants who have not progressed at 12 months (PFS12)
The proportion of participants who have not demonstrated radiographic progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or demonstrated clinical progression-free survival (PFS) at 12 months after the start of study treatment. Twelve-month landmark PFS rate will be obtained with 95% confidence interval using the Kaplan-Meier method.
Percentage of participants with Skeletal Related Events (SRE)
The percentage of participants who demonstrate an SREs defined as: 1) pathological fracture; 2) surgery or radiation to the bone; or 3) cord compression, by bone scan will be reported
Percentage of participants with osteonecrosis of the jaw (ONJ)
The percentage of participants who demonstrate ONJ, by clinical exam will be reported.
Percentage of participants with reported treatment-related, systemic, adverse events
The percentage of participants with treatment-related, systemic toxicity of any grade as classified by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be reported.
Median PFS
PFS is defined as the time from day of study treatment initiation (C1D1) until evidence of disease progression per RECIST v1.1 criteria, in patients with measurable disease at baseline, or death from any cause. Participants will be censored for PFS at the start of any subsequent therapy or at last negative scan if there is no evidence of disease progression. The median PFS in months will be reported with a 95% confidence interval.
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Kelly Fitzgerald, MD
Lead sponsor
University of California, San Francisco
Sponsor institution
Exelixis
Collaborator
