Real-life efficacy of nivolumab plus ipilimumab combination in untreated, unresectable malignant pleural mesotheliomas: Result of French early access program-MESOIMMUNE - GFPC 04-2021.

8536 Background: The SOC for unresectable malignant pleural mesothelioma (MPM) has changed in 2020 with the combination nivolumab plus ipilimumab (NIVO+IPI) results of CheckMate 743 study. As CheckMate 743 was therapeutic trial in selected MPM patients (pts), additional data would be of interest to confirm the results in real-life setting. Methods: The present multicenter, retrospective study assessed the outcomes of NIVO+IPI, via an early access program (EAP) in France, in pts with treatment naïve unresectable MPM. The primary objective was investigator-assessed real world progression-free survival (rwPFS) from initiation of NIVO+IPI, defined as time from first dose of NIVO+IPI to first documentation of objective disease progression or death from any cause. The secondary objectives were real world OS (rwOS), objective response rate (ORR), and safety of NIVO+IPI combination. Results: From April 1, 2021 to Feb 15, 2022 (last day of EAP) there were 143 pts included out of 350 pts treated by EAP for unresectable MPM in 44 centers. Population characteristics are described in the table. With a median follow-up of 14.1 months, median rwPFS was 7.8 months (95%CI 6.2-9.5). rwPFS rates no differ according to histological subtypes: rwPFS for epithelioid MPM was 8.1 months (95%CI 6.0-12.6) and 7.4 months (95% CI 5.3-11.2) for other histological subtypes. The median rwOS was not reached (NR), 1-year survival rate was 65% (95% CI 57-75%). Median rwOS was NR and 13.1 (95% CI 7.8- NA) in epithelioid and non-epithelioid MPM, respectively. At 1 year, 71.2% of pts with epithelioid MPM are still alive versus 51.2% in pts with other histological subtypes. ORR was 23.9% (95% CI 16.9-32.0%) with median time to response of 3.68 months (2.33-5.09) after introduction of NIVO+IPI. Disease control rate was 80.4%. Grade 3-4 adverse events (AE) occurred in 37.8%. Severe immune-related AE occurred in 13.9% of patients. Five deaths were associated with treatment-related AEs according to investigators judgment. Conclusions: While pt’s characteristics differed from the pivotal trial, notably with older and unselected patients, efficacy outcomes that we observed here compares favorably with CheckMate 743 results. Tolerance looks acceptable in real-life setting despite 5 toxic deaths reported. Extended follow-up of our cohort will allow consolidation of the results. Clinical trial information: NCT05308966 . [Table: see text]