LAUSR

4567 Background: Drug combinations targeting vascular endothelial growth factor (VEGF) and the programmed death one (PD-1) pathway have demonstrated encouraging efficacy in patients (pts) with mRCC. We are conducting a phase I/II trial combining the VEGF-targeting tyrosine kinase inhibitor (TKI) axi and the PD-1 inhibitor nivo in mRCC pts. Methods: The phase I portion of this investigator-initiated, multi-center trial enrolled pts with TKI-refractory mRCC (any line) and no prior anti-PD-1. It used a 3+3 design, with axi dosing starting at 3 mg orally BID, escalating to a target dose of5 mg BID. Nivo dosing was fixed at 240 mg IV Q2 weeks or 480 mg Q4 weeks. Eligible pts received axi alone for a one week induction, followed by combination dosing. There was a 4 week period to assess for dose limiting toxicities (DLTs). The primary endpoint for phase I was safety and establishment of a recommended phase II dose (RP2D) for axi. Safety and early efficacy data for the phase I cohort are presented. Results: Twelve pts received treatment during the phase I portion, with all evaluable for toxicity. Ten were 2nd line and 2 were 3rd line or beyond. One DLT was noted in the first cohort of three pts (grade 3 autoimmune disorder), thus that cohort was expanded. No further DLTs were reported at axi 3 mg BID, or at further expansion to 5 mg BID. Grade 3 adverse events (AEs) at least possibly related to one of the drugs included expected side effects HTN, hyperglycemia, and transaminitis. One patient received steroids for an immune related AE (grade 3 transaminitis) that resolved to grade 1 with steroids. No grade 4-5 AEs occurred. Axi at 5 mg BID was chosen as the RP2D. With 10 pts evaluable for efficacy, 4 pts had partial responses, 4 pts had stable disease, and 2 had progressive disease. Updated efficacy data will be presented. Conclusions: The phase I portion of this phase I/II trial has demonstrated expected safety and established 5 mg BID as the RP2D axi dose. This ongoing VEGF TKI/PD1 trial incorporating two drugs already approved for mRCC pts has shown encouraging signs of efficacy and has now expanded to include treatment naïve pts in addition to TKI-refractory pts as part of phase II. Clinical trial information: NCT03172754.