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

Abstract

and PFS (RECIST v1.1; blinded, independent central review) were assessed by the stratified log-rank test in the ITT population. The protocol-specified first interim analysis (IA1) was planned to occur when w255 deaths occurred and w12 months after the last participant was randomized. Nonbinding futility criteria at IA1 were differences in the restricted mean survival time (RMST) between pembroeipi and pembroeplacebo of 0.2 at the maximum observation time and 0.1 at 24 months of follow-up. Results: Between 12-January-2018 and 22-August-2019, 568 participants were randomized to pembroeipi (n¼284; 282 treated) and pembroeplacebo (n¼284; 281 treated). As of 01-September-2020, median (range) study follow-up was 20.6 months (12.4-31.7), treatment was ongoing in 21.3% in the pembroe ipi arm vs 23.8% in the pembroeplacebo arm, and median number of treatment cycles was 10 vs 15. Baseline characteristics were balanced between arms. With 272 deaths, median OS was 21.4 months for pembroeipi vs 21.9 months for pembroeplacebo (HR, 1.08 [95% CI, 0.85-1.37]; P ¼ 0.74). RMST differences were e0.56 at the maximum observation time and e0.52 at 24 months, which met the futility criteria. With 372 events, median PFS was 8.2 months for pembroeipi vs 8.4 months for pembroeplacebo (HR, 1.06 [95% CI, 0.86-1.30]; P ¼ 0.72). ORR was 45.4% in both arms; median DOR was 16.1 months for pembroeipi vs 17.3 months for pembroeplacebo. Treatment-related AEs occurred in 76.2% of pembroeipi recipients vs 68.3% of pembroeplacebo recipients, were of grade 3-5 in 35.1% vs 19.6%, led to death in 2.5% vs 0%, and led to discontinuation of any treatment in 25.2% vs 10.7%. Immune-mediated AEs and infusion reactions occurred in 44.7% of pembroeipi recipients vs 32.4% of pembroe placebo recipients, were grade 3-5 in 20.2% vs 7.8%, led to death in 2.1% vs 0%, and led to discontinuation of any treatment in 14.9% vs 5.3%. Based on the observed efficacy and safety, the external data monitoring committee recommended that the study be stopped due to futility and that participants discontinue ipi/placebo. Conclusion: Adding ipilimumab to pembrolizumab does not improve efficacy and is associated with greater toxicity than pembrolizumab alone as first-line therapy for metastatic NSCLC with PD-L1 TPS 50% and no targetable EGFR or ALK aberrations. These data confirm pembrolizumab monotherapy as a standard-of-care for this population.

Oncological Frontiers in the Treatment of Malignant Pleural Mesothelioma

“…In the NivoMes phase 2 study, a population of 38 patients with relapsed MPM was treated with nivolumab 3 mg/kg q14, obtaining a 3-month DCR of 50% and an ORR of 24%. The role of nivolumab as a salvage therapy was confirmed by the phase 2 MERIT trial and, most recently, by the phase 3 placebo-controlled CONFIRM trial: 332 patients were randomized 2:1 to nivolumab 240 mg q14 or placebo, stratified by histology (epithelioid vs. non epithelioid); the study met its two co-primary endpoints, showing an investigator-assessed mPFS of 3.0 vs. 1.8 months (HR 0.62, p < 0.001) and an investigator-assessed mOS of 9.2 vs. 6.6 months (HR 0.72, p = 0.02) in favor of nivolumab [ 25 , 26 , 27 ].…”

Immunotherapeutic Approaches in Malignant Pleural Mesothelioma

“…Preliminary data from this study showed the safety of the treatment and proved that nivolumab improved both PFS rates at 12 months of treatment (14.5 in the nivolumab arm vs. 4.9 for placebo) and OS (9.2 months vs. 6.6). The significant clinical benefits were more evident for the epithelioid subtype [ 31 ].…”

Systemic Treatments for Unresectable Pleural Mesothelioma: A Review of the Literature

“…There was no statistically significant association between survival and PD-L1 status. 25 To prove, once more the importance of biomarker-based treatment selection, the randomized, phase III PROMISE-meso trial evaluated pembrolizumab versus standard chemotherapy in MPM patients. Patients were randomized (1:1) into two arms: one received pembrolizumab (200 mg i.v.…”