Standard Versus Modified Ipilimumab, in Combination With Nivolumab, in Advanced Renal Cell Carcinoma: A Randomized Phase II Trial (PRISM)

Naveen s. Vasudev*, Gemma Ainsworth, Sarah Brown, Lisa Pickering, Tom Waddell, Kate Fife, Richard Griffiths, Anand Sharma, Eszter Katona, Helen Howard, Galina Velikova, Anthony Maraveyas, Janet Brown, Carmel Pezaro, Mark Tuthill, Ekaterini Boleti, Amit Bahl, Bernadett Szabados, Rosamonde e. Banks, Joanne BrownBalaji Venugopal, Poulam Patel, Ankit Jain, Stefan n. Symeonides, Paul Nathan, Fiona j. Collinson, Thomas Powles

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Ipilimumab (IPI), in combination with nivolumab (NIVO), is an approved
frontline treatment option for patients with intermediate- or poor-risk ad-
vanced renal cell carcinoma (aRCC). We conducted a randomized phase II trial to
evaluate whether administering IPI once every 12 weeks (modified), instead of
once every 3 weeks (standard), in combination with NIVO, is associated with a
favorable toxicity profile.

Treatment-na¨ıve patients with clear-cell aRCC were randomly assigned 2:1 to
receive four doses of modified or standard IPI, 1 mg/kg, in combination with
NIVO (3 mg/kg). The primary end point was the proportion of patients with a grade 3-5 treatment-related adverse event (trAE) among those who received at least one dose of therapy. The key secondary end point was 12-month progression-free survival (PFS) in the modified arm compared with historical sunitinib control. The study was not designed to formally compare arms for efficacy.

Between March 2018 and January 2020, 192 patients (69.8% intermediate/
poor-risk) were randomly assigned and received at least one dose of study
drug. The incidence of grade 3-5 trAEs was significantly lower among partic-
ipants receiving modified versus standard IPI (32.8% v 53.1%; odds ratio, 0.43
[90% CI, 0.25 to 0.72]; P 5 .0075). The 12-month PFS (90% CI) using modified
IPI was 46.1% (38.6 to 53.2). At a median follow-up of 21 months, the overall
response rate was 45.3% versus 35.9% and the median PFS was 10.8 months
versus 9.8 months in the modified and standard IPI groups, respectively.

Rates of grade 3-5 trAEs were significantly lower in patients receiving modified
versus standard IPI. Although 12-month PFS did not meet the prespecified efficacy threshold compared with historical control, informal comparison of treatment groups did not suggest any reduction in efficacy with the modified schedule.
Original languageEnglish
JournalJournal of Clinical Oncology
Publication statusPublished - 6 Nov 2023


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