The following is a summary of “Standard Versus Modified Ipilimumab, in Combination With Nivolumab, in Advanced Renal Cell Carcinoma: A Randomized Phase II Trial (PRISM),” published in the November 2023 issue of Oncology by Vasudev, et al.

For a randomized phase II trial, researchers sought to assess whether administering ipilimumab (IPI) once every 12 weeks (modified schedule) in combination with nivolumab (NIVO) would result in a more favorable toxicity profile compared to the standard schedule of once every 3 weeks in treatment-naïve patients with intermediate- or poor-risk advanced renal cell carcinoma (aRCC).

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

Between March 2018 and January 2020, 192 patients were enrolled. The incidence of grade 3-5 trAEs was significantly lower in participants receiving modified IPI than standard IPI (32.8% vs. 53.1%; odds ratio, 0.43 [90% CI, 0.25 to 0.72]; P = .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%, with a median PFS of 10.8 months.

The study concluded that the modified IPI schedule was associated with significantly lower rates of grade 3-5 trAEs. Although the 12-month PFS did not meet the prespecified efficacy threshold compared to historical control, there was no apparent reduction in efficacy with the modified schedule in the informal comparison of treatment groups.

Source: ascopubs.org/doi/10.1200/JCO.23.00236