All subjects will receive zanzalintinib 100mg orally (PO) once daily plus nivolumab standard of care dosing (i.e., 240mg IV every 2 weeks or 480mg IV every 4 weeks) for a total of 12 weeks, followed by restaging scan/evaluation for surgical operability and an adaptive approach that includes (1) surgical resection if the participant is eligible for surgery (Cohort A), (2) up to 48 weeks total (from Cycle 1 Day 1) of zanzalintinib plus nivolumab if the participant has partial response or stable disease but remains inoperable (Cohort B1), or (3) stopping protocol mandated treatment to receive standard of care systemic therapy and continue follow up per protocol if the participant has disease progression (Cohort B2).
Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
Age ≥ 18 years at the time of consent.
Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 within 30 days prior to registration.
Histologically confirmed (i.e., tissue from primary kidney tumor of interest) diagnosis of clear cell renal cell carcinoma with or without sarcomatoid features. NOTE: biopsy should be performed at least 5 days before the first dose of study treatment and must be completely healed before dosing.
Non-clear cell histology.
Measurable metastatic disease per RECIST 1.1 criteria and other non-measurable lesions including bone metastasis, leptomeningeal disease, lymphangitic involvement of lung or skin, pathologically confirmed-malignant ascites/pleural/pericardial effusion.
Prior systemic therapy, including zanzalintinib, nivolumab and other vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs)/immune checkpoint inhibitors(IOs), for the treatment of renal cell carcinoma.
Prior surgery and/or radiation to the primary renal cell carcinoma tumor of interest. NOTE: prior surgery and/or radiation to other areas of the kidney (i.e., prior small kidney tumor resection or radiation) is allowed if > 4 weeks before first dose of study treatment.
Single group
Zanzalintinib
DrugZanzalintinib 100mg orally (PO) once daily for 12 weeks up (all subjects) and up to 48 weeks from Cycle 1 Day 1 (Cohort B1)
Nivolumab
DrugNivolumab will be administered at either 240mg IV every 2 weeks or 480mg IV 4 every weeks for 12 weeks (all subjects) and up to 48 weeks from Cycle 1 Day 1 (Cohort B1).
Objective response rate (ORR)
ORR will include complete response (CR) + confirmed partial response (PR) and will be determined as per RECIST version 1.1.
Conversion from inoperable to operable
Conversion from inoperable to operable state will be indicated by percentage of subjects who were considered surgically challenging/inoperable per surgeon discretion at enrollment who subsequently undergoing surgical resection.
Number of Participants with Adverse Events
Adverse events will be assessed according to the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5
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Qian Qin
Lead sponsor
Hoosier Cancer Research Network
Sponsor institution
Exelixis
Collaborator
University of Texas
Collaborator
