Phase 1 cabozantinib multi-kinase (MET/AXL/VEGFR2) inhibitor + nivolumab PD-1 mAb

MD Anderson’s Phase 1 proof-of-concept study tests whether cabozantinib plus nivolumab reshapes the bone immune microenvironment in clear cell renal cell carcinoma (ccRCC) with bone metastases, using paired baseline and on-treatment core biopsies as the key translational readout. After completing baseline biopsies, participants receive standard-of-care systemic therapy with oral cabozantinib (Exelixis; small-molecule multi-kinase inhibitor targeting MET, AXL, VEGFR2, RET and other kinases) combined with IV nivolumab every 4 weeks (Bristol Myers Squibb; PD-1–blocking monoclonal antibody that reinvigorates antitumor T cells). The main scientific angle is tissue-based pharmacodynamics in a hard-to-sample compartment (bone), aiming to connect clinical therapy to immune composition and activation states that may underlie skeletal events and resistance. Eligible patients are adults with advanced/metastatic ccRCC involving bone; ccRCC commonly develops osseous disease, and bone metastases remain a major morbidity driver. In routine practice today, first-line metastatic ccRCC care is typically an immune checkpoint inhibitor + VEGF-pathway TKI combination (or IO/IO in selected patients), with bone-directed agents and/or local radiation used to reduce fracture/spinal cord compression risk; this study asks what the cabozantinib+nivolumab regimen is doing inside bone to inform better sequencing and supportive strategies.