Neoadjuvant Zanzalintinib Plus Nivolumab in Patients With Locally Advanced and/or Inoperable Clea… (NCT06794229) | Clinical Trial Compass
RecruitingPhase 2
Neoadjuvant Zanzalintinib Plus Nivolumab in Patients With Locally Advanced and/or Inoperable Clear Cell Renal Cell Carcinoma With or Without Non-measurable Metastasis
United States69 participantsStarted 2025-10-30
Plain-language summary
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).
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. 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.
✓. Locally advanced (cT3/T4, N0-1) OR deemed surgically inoperable (per surgeon discretion based on factors including but not limited to surgical challenge and/or medical co-morbidities, such as renal functional reserve). Satisfying either of the criteria allows for enrollment.
✓. Non-measurable soft tissue metastasis with longest diameter \< 10mm or pathological lymph nodes \< 15 mm in short axis are allowed.
✓. Recovery to baseline or Grade ≤ 1 severity (CTCAE v5) from adverse events (AEs) related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy (eg, physiological replacement of corticosteroid). Low-grade or controlled toxicities such as alopecia, Grade ≤ 2 hypomagnesemia, Grade ≤ 2 neuropathy are permitted).
✓. Adequate organ and marrow function, based upon meeting all the following laboratory criteria within 30 days before first dose of study treatment:
Exclusion criteria
✕. 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.
✕. Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin inhibitors) and platelet inhibitors (eg, clopidogrel). NOTE: For prohibited anticoagulants, subjects must have discontinued the anticoagulant within 3 days or 5 half-lives prior to first dose of study treatment, whichever is longer. Allowed anticoagulants are the following:
✕. Use of any complementary medications (eg, 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:
✕. Clinically significant hematuria, hematemesis, or hemoptysis of \> 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose of study treatment.