A pilot randomized study evaluating nivolumab (nivo) or nivo + bevacizumab (bev) or nivo + ipilimumab (ipi) in patients with metastatic renal cell carcinoma (MRCC) eligible for cytoreductive nephrectomy (CN), metastasectomy (MS) or post-treatment biopsy (Bx).

4520Background: Since ipi and nivo use distinct mechanisms for T cell activation and bev promotes antigen presentation, we hypothesize that nivo+bev or nivo+ipi would safely lead to measurable immunologic changes and improved clinical activity in MRCC. Methods: In this open-label, randomized trial (NCT02210117), adults with MRCC w/o prior immune checkpoint therapy and anti-VEGF therapy were enrolled and randomized 2:3:2 to receive nivo, nivo+bev or nivo+ipi, followed by surgery (CN or MS), or Bx, and subsequent nivo maintenance therapy up to 2 years. Response was assessed at ≥12 weeks. Pre- and post-treatment blood and tumors were obtained for correlative studies. Results: One hundred patients have been accrued and 90 are evaluable for responses (table below, W = withdrawal; BOR = Best overall response; BRES = Best Response excluding surgical effect). Clinical trial information: NCT02210117. BOR was 50% complete response (CR) + partial response (PR) nivo, 48% CR+PR nivo+bev, 39% CR+PR nivo+ipi. For patien...