Beschreibung:
<jats:p> 446 </jats:p><jats:p> Background: Several PD-1 immune-checkpoint inhibitors including Nivolumab (Nivo) are approved in urothelial cancer. Recently, in the front line setting, improved activity of combined PD-L1 and CTLA4 immune-checkpoint inhibition has been reported and a phase III trial with Nivolumab + Ipilimumab (Nivo+Ipi) is ongoing. Here we report a response-based tailored approach starting treatment with Nivo monotherapy using Nivo+Ipi as immunotherapeutic “boost”. Methods: Between July 2017 and April 2019 86 patients were enrolled and treated according to protocol version 3 (cohort 1). Patients started with Nivo 240 mg Q2W induction. After 4 dosings and tumor assessment at week 8 (i) responders (PR/CR) to Nivo monotherapy continued with maintenance while (ii) patients with stable (SD) or progressive disease (PD) received 2 cycles Nivo3+Ipi1 followed by another 2 cycles Nivo1+Ipi3 if not responding. Median follow-up is 8.7 months. The primary endpoint is confirmed investigator-assessed objective response rate (ORR) per RECIST1.1. Secondary endpoints include activity of Nivo monotherapy at week 8, remission rate with Nivo+Ipi “boosts”, safety, overall survival and quality of life. Results: Of the patients 42, 39 and 5 were first, second and third line, respectively. Median age was 67 years (range 45-84), 61 patients (71 %) were male and 25 female. ORR with Nivo monotherapy at first assessment (week 8) was 29 % and 23 % in first and second/third line, respectively. Of the patients 41 received Nivo+Ipi “boosts” after week 8 while 12 received later “boosts”. Best overall response (BOR) rate with Nivo induction ± Nivo+Ipi “boosts” was 48 % and 27 % in first and second/third line, respectively. In first line 7/17 (41 %) patients receiving Nivo+Ipi after week 8 had an improved response compared to 2/24 (8.3 %) in second/third line. Of the patients who continued with Nivo maintenance after week 8 and received later “boosts” 2/12 (17 %) had a PR and 2/12 (17 %) improved to SD. Treatment-related AEs will be presented. Conclusions: TITAN–TCC explores a response-driven use of Nivo+Ipi as an immunotherapeutic “boost”. In first line, this significantly improved ORR compared to the expected response rate of Nivo monotherapy, providing further evidence to the added value of Ipi in combination with Nivo. Further follow-up is ongoing to characterize duration and depth of response. Clinical trial information: NCT03219775 . Research Sponsor: Bristol-Myers Squibb[Table: see text] </jats:p>