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Modified ipilimumab schedule reduces risk of grade 3/4 adverse events

Presented By
Dr Naveen Vasudev, St James University Hospital, UK
ESMO 2021
Phase 2, PRISM
First results of the randomised, phase 2 PRISM trial showed that ipilimumab every 12 weeks, instead of every 3 weeks, in combination with first-line nivolumab significantly reduced rates of grade 3/4 adverse events in patients with advanced renal cell carcinoma (RCC).

Ipilimumab/nivolumab is an approved and standard first-line treatment for patients with intermediate and poor-risk advanced RCC. Ipilimumab/nivolumab has proven to significantly increase overall survival (OS) versus sunitinib in patients with intermediate or poor risk advanced RCC [1]. However, grade 3/4 treatment-related adverse events are relatively common during the initial combination period. Therefore, the randomised, phase 2 PRISM trial (EudraCT 2017-001476-33) aimed to determine whether modified scheduling of ipilimumab, in combination with nivolumab, is associated with improved tolerability, whilst maintaining treatment efficacy in line with previous comparative studies with sunitinib. Dr Naveen Vasudev (St James University Hospital, UK) presented the first results of PRISM [2].

A total of 192 patients (69.8% intermediate/poor-risk) were randomised 1:2 to receive 4 doses of ipilimumab (1 mg/kg) every 3 weeks (conventional) or every 12 weeks (modified), in combination with nivolumab (3 mg/kg), until disease progression or unacceptable toxicity.

The primary endpoint was the proportion of patients with a grade 3/4 treatment-related adverse events within 12 months of initiating treatment. Secondary endpoints included progression-free survival (PFS) at 12 months – tested against historical PFS associated with sunitinib – and objective response rate (ORR). The primary endpoint was met: significantly fewer grade 3/4 adverse events occurred in the modified arm than in the conventional arm (32.8% vs 53.1%; OR 0.43; P=0.0075). In particular, arthralgia and colitis were less observed in the modified arm. Also, discontinuation due to adverse events was reduced in the modified arm (22.7% vs 39.1%).

PFS rate at 12 months was 46.1% versus 39.7% in the historical control. Kaplan-Meier PFS- and OS-curves were comparable in the modified and conventional arms. “Giving ipilimumab every 12 instead of every 3 weeks led to a significant reduction in grade 3/4 treatment-related events and therefore supports further exploration of different ipilimumab/nivolumab regimens,” concluded Dr Vasudev.

  1. Motzer RJ, et al. N Engl J Med. 2018;378:1277–1290.

  2. Vasudev NS, et al. Nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced renal cell carcinoma: A randomized phase II trial (PRISM). Abstract LBA29, ESMO Congress 2021, 16–21 September.


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