LBA75 - Prospective randomised phase-II trial of ipilimumab/nivolumab versus standard of care in non-clear cell renal cell cancer: Results of the SUNNIFORECAST trial

Background

Non-clear cell renal cell cancers (nccRCC) are a rare and heterogeneous group of more than 20 histological and molecular defined entities. The rarity of these entities contributed to the dearth of large randomized trials and uncertainties for optimal treatment recommendations. Here, we report the final results of the prospective randomised European trial SUNNIFORECAST in therapy-naïve patients with advanced nccRCC.

Methods

We randomly assigned patients (pts) with nccRCC in a 1:1 ratio to receive either nivolumab 3 mg/kg IV combined with ipilimumab 1 mg/kg IV every 3 weeks for 4 doses followed by a flat dose of 240 mg IV every 2 weeks or 480 mg every 4 weeks versus SOC by investigators choice until disease progression or intolerance occurred. Pts were stratified in papillary vs. non-papillary nccRCC and according to the IMDC risk score. Central pathology was mandatory to confirm the diagnosis and nccRCC subtype according to the WHO classification 2022. The primary endpoint was OS rate at 12 mos.

Results

A total of 316 pts were screened in 7 European countries and 31 centers. The randomized population of 309 pts (70.9% male, 29.1% female) - randomized to receive either nivolumab plus ipilimumab (157 pts) or SOC (152 pts; 124 x TKI, 17 x TKI/IO, 2x others, 9 pts did not receive any study medication). 178 pts (57.6%) had papillary, 60 pts (19.4%) a chromophobe, 12 pts (3.9%) a MIT, 9 (2.9%) a collecting duct carcinoma and 50 had other subtypes. According to the IMDC score, 23.9% were of low, 51.8% of intermediate and 24.3% of high risk. The 12 mos OS rate for the entire population was 82.5%. The 12 mos OS rate for Nivo/Ipi 86.9% (95%-CI 80.2%-91.5%) was statistically significant superior to the SOC 76.8% (95%-CI 68.6%-83.1%) (p=0.014). Median OS was 42.4 mos for the Ipi/Nivo arm and 33.9 mos for the SOC arm. The ORR of 25.4% [ 95%-CI 15.8, 37.1] vs. 23.3% [ 15.1, 33.4]) and the median PFS of 5.09 [2.91–6.05] mos vs 5.55 [5.29–7.21) mos was not statistically significant different between Nivo/Ipi and SOC.

Conclusions

OS rate at 12 mos was significantly higher with nivolumab plus ipilimumab than with SOC in nccRCC pts. Additionally, pts in the Nivo/Ipi arm had a longer median OS, especially in the papillary high-risk group.

Clinical trial identification

EudraCT 2016-000706-12; NCT03075423.

Editorial acknowledgement

Legal entity responsible for the study

Goethe University Frankfurt, Germany.

Funding

Bristol Myers Squibb (BMS).

Disclosure

L. Bergmann: Financial Interests, Institutional, Funding: Bristol Myers Squibb. All other authors have declared no conflicts of interest.