Tailored immunotherapy approach with nivolumab in advanced renal cell carcinoma (TITAN-RCC)

Abstract

Background: Nivolumab (N) þ ipilimumab (I) has been approved for the 1 st line treatment of IMDC intermediate and poor risk advanced RCC. However, administration of NþI in a fixed regimen with 4 induction cycles may result in more treatment related adverse events (AEs) compared with N alone. It is hypothesized that a tailored approach starting treatment with N alone and using NþI as immunotherapeutic boost will improve efficacy outcomes as compared to N alone and reduce AEs. Methods: This multicentric European study enrolled 258 1 st and 2 nd line (after TKI) pts with IMDC intermediate and poor risk, advanced clear cell RCC between Oct. 2016 and Dec. 2018. Pts started with N 240 mg Q2W induction. Pts with early significant PD (week 8) or either SD or PD at week 16 received 2-4 NþI boost cycles. Responders (PR/ CR) to N monotherapy continued with maintenance with NþI boosts only for progression. The primary endpoint is confirmed investigator assessed objective response rate (ORR) per RECIST independent in 1 st and 2 nd line. Secondary endpoints include activity of N monotherapy, remission rate with NþI boosts, safety, overall survival and QoL. Results: 108 1 st and 99 2 nd line pts were analyzed for efficacy. Median age was 65 y (range 20-87). 70 % were intermediate and 27 % poor risk. Confirmed ORR with 1 st line N monotherapy was 28.7 % (95 % CI 20-38). Best overall response (BOR) after N induction 6 NþI boosts was 37 % (95 % CI 28-47) and 28 % (95 % CI 20-38) in 1 st and 2 nd line, respectively. 102 pts received NþI boosts for either SD (n ¼ 35) or PD (n ¼ 67) until week16. Of these, 12 (12 %) and 54 (53%) had a PR/CR and SD, respectively. Two (6%) pts entering boosts for SD had PD afterwards compared to 51% with early PD. Treatment-related AEs will be presented.