PS01.11 Nivolumab Versus Placebo in Relapsed Malignant Mesothelioma: The CONFIRM Phase 3 Trial

Abstract

Malignant mesothelioma (MM) is an intractable cancer. No therapy has yet shown an improvement in overall survival following standard first line chemotherapy doublet comprising pemetrexed and cisplatin or carboplatin since it was licensed in 2004. Nivolumab is a programmed death-1 (PD-1) inhibitor that has shown activity in previously-treated MM in two single arm phase II clinical trials. Here we report results of the Stand-Up-To-Cancer Cancer Research UK CONFIRM trial (NCT03063450), a double blind phase 3 randomized study of nivolumab versus placebo in patients with unresectable MM. We are reporting preliminary data based on the recommendation of the independent data monitoring committee and trial steering committee. Adult patients with previously treated, unresectable, histologically confirmed MM (pleural or peritoneal) and ECOG performance status 0–1 were randomized (2:1 ratio) to nivolumab (3 mg/kg) or placebo once every 2 weeks until disease progression or a maximum of 12 months. Participants were stratified by epithelioid vs non-epithelioid histology. The co-primary endpoints were investigator-assessed progression-free survival (PFS) and overall survival (OS); key secondary endpoints included best overall response. Exploratory endpoints included safety and tolerability. PDL1 tumour proportion score (Dako22C3) was evaluated on all available tumour blocks. Between 10/05/2017 and 30/03/2020, 332 participants were randomised to nivolumab (n=221) or placebo (n=111). Baseline characteristics were balanced between arms, where 87% of participants had an epithelioid histology and 96% were were 3rd line or greater. OS was immature but showed longer survival with nivolumab (events 232 [target 291]; median, 9.2 vs 6.6 months; HR, 0.72; 95% CI, 0.55–0.94; P=0.02). Investigator-assessed PFS (time-to-event) was longer for nivolumab vs placebo (events=309; median, 3.0 vs 1.8 months; HR 0.62; 95% CI, 0.49–0.78; P<0.001). Both were statistically significant under the Fallback procedure for maintaining overall type 1 error. Grade 3-4 treatment-related adverse events were reported in 19% on nivolumab and in 6.3% on placebo. Treatment discontinuation due to toxicity occurred in 13.1% (nivolumab) versus 2.7% (placebo). Predictive and prognostic significance of PDL1 TPS and outcome by histology will be presented. CONFIRM met its co-primary endpoints of improved OS and PFS with nivolumab vs placebo in relapsed MM. The safety profile of nivolumab was consistent with its known profile with no new safety signals. Nivolumab monotherapy is an effective treatment option for relapsed MM.