Treatment-free survival (TFS) outcomes from the phase II study of nivolumab and salvage nivolumab + ipilimumab in advanced clear cell renal cell carcinoma (aRCC) (HCRN GU16-260-Cohort A).

604 Background: Treatment with immunotherapy can be associated with prolonged disease control after discontinuation without the need for further anticancer therapy. Toxicity from therapy can also persist after cessation. TFS with and without toxicity can characterize survival time. Significant TFS was reported for CheckMate 067 trial in pts with metastatic melanoma (Regan et al JITC 2021) and CheckMate 214 trial for pts with aRCC (Regan et al CCR 2021), but treatment was often halted for toxicity rather than a pre-defined treatment endpoint. We therefore sought to assess TFS in the HCRN GU16 260 trial, which was designed to reduce toxicity and to cap immunotherapy duration (Atkins et al JCO 2022). Methods: Data were analyzed from 128 patients (pts) with clear-cell aRCC treated with first-line nivolumab (NIVO) monotherapy for up to 2 years. As part of the protocol, salvage nivolumab/ipilimumab (NIVO/IPI) for up to 1 year was provided to eligible patients with disease progression at any point or stable disease at 48 weeks (28% of pts). TFS was defined as the area between Kaplan-Meier curves for time from registration to protocol therapy cessation and for time from registration to subsequent therapy initiation or death, estimated from 36-month (mo) mean times. The time on treatment or off treatment with grade 3+ treatment-related adverse events (TRAEs) was also captured. Results: At 36 mos from enrollment, 68.3% of pts were alive: 96.8% of IMDC favorable-risk (FAV) pts and 56.6% of those with intermediate/poor-risk (I/P), respectively. The 36-mo mean time on protocol therapy was 11.5 mos (16.0 mos for FAV pts and 9.6 mos for I/P pts). The 36-mo mean TFS for the whole population was 9.4 mos. For FAV pts the mean TFS was 12.9 mos, of which TFS with grade 3+ TRAEs was 1.5 mos. For I/P pts, the mean TFS was 8.0 mos, of which TFS with grade 3+ TRAEs was 1.0 mos. At 36 mos, 65.6% of FAV pts and 27.1% of I/P pts were alive and second-line treatment-free. Conclusions: NIVO monotherapy with salvage NIVO/IPI in non-responders is an active treatment approach in treatment-naïve pts with aRCC and results in substantial TFS and toxicity-free TFS. TFS was particularly noted in pts with FAV disease, further supporting the use of an immunotherapy-only regimen in this population. Clinical trial information: NCT03117309 . [Table: see text]