Sequential immunotherapy in rare variant renal cell carcinomafinal report of UNISoN (ANZUP 1602): Nivolumab then ipilimumab + nivolumab in advanced nonclear cell renal cell carcinoma.

Abstract

4537 Background: Immune checkpoint immunotherapy (ICI) is active against many cancers. Many people are failed by PD1 inhibition alone, but not all patients benefit, nor require combination ICI treatment. UNISoN (NCT03177239) previously reported outcomes in people with non-clear cell renal cell carcinoma (nccRCC) receiving nivolumab (N) monotherapy, and N plus ipilimumab (I) in those whose cancers progressed after N alone. We present the final planned report. Methods: Population, Intervention, Analysis: Participants (pts) with advanced nccRCC with good performance status (ECOG 0/1) received N 240mg q2w alone (Part 1). Those with cancers refractory to N at 3 months were offered combination I (1mg/kg) + N (3mg/kg) q3w for up to 4 doses, followed by N 240mg q2w for a maximum total of 12 months of N (Part 2). UNISoN was powered to identify a clinically-relevant objective tumor response rate (OTRR) of 30% (assuming 15% was not relevant) among people receiving I+N in Part 2. Results: 85 pts with a representative spectrum of nccRCC histologies were enrolled and received N. Amongst the total population enrolled to UNISoN Part 1/2, mOS was 24 (16-28) months and 12m OS was 65% (54%-74%); of those proceeding to Part 2, the mOS was 10 (6-17) months only. Overall, 17% (10%-27%; 14/83) and 10% (3%-23%; 4/41) of pts experienced a response from N alone or I+N, respectively. 41 pts refractory to N received I+N. Overall in Part 2, the median time on treatment was 2.1 (95% CI 1.8, 2.8) months, the median number of cycles was 3; median follow-up at final analysis was 22 (16-30) months. In this population, the median PFS was 2.6 (2.2-3.8) months and 12m PFS was 11% (4%-23%). 13% (7%-22%) of patients were free of progression or death at 24 months. The primary endpoint was not met; only 80% of pts failed by N were assessable for response in Part 2. Overall tumor responses from N alone or I+N were more common in pts with papillary histology; pts with chromophobe histology had poor outcomes. No late toxicity safety signals were observed. Conclusions: Some pts with nccRCC benefit from N alone, or addition of I when disease is inadequately controlled by N alone, however most pts have limited benefit from ICI. More effective therapeutic options are needed for the majority of people with rare variant renal cell carcinomas. Novel markers of response are required to more rapidly predict pts who will progress on N. Translational research to identify predictive biomarkers of response is ongoing. Clinical trial information: NCT03177239.