Second or 3rd line nivolumab (Nivo) versus nivo plus ipilimumab (Ipi) in malignant pleural mesothelioma (MPM) patients: Updated results of the IFCT-1501 MAPS2 randomized phase 2 trial

Abstract

Background: No treatment is currently recommended inMPMpts progressing after 1st-line pemetrexed platinum doublet. Disease control rate (DCR) is<30% with all drugs tested in this setting. Anti-PD1 or anti-PD-1 plus anti-CTLA-4 combo efficacy deserves confirmation in MPM. Methods: Multicenter randomized non-comparative phase 2 trial. Eligible pts: age>18, PS 0-1, histologically provedMPM relapsing after 1 or 2 prior lines including pemetrexed/ platinum doublet, measurable disease. Randomized pts (1:1) received Nivo 3 mg/kg q2w, or Nivo 3 mg/kg q2w plus Ipi 1 mg/kg q6w, until progression or unacceptable toxicity. Primary endpoint was DCR at 12 weeks. Results: From April to August 2016, 125 pts were accrued in 20 centers. Males: 80%, median age: 71.8 years (range 32.5-88.1), PS 1: 62.4%, epithelioïd 83.2%, 1 previous line: 69.6%.70%of pts received at least 3 cycles of either treatment. 12 weeks-DCR assessed by BICR in the first 108 pts was 44.4% [CI95%: 31.2-57.7%] with Nivo (n=54), and 50.0% [36.7-63.3%] with Nivo+Ipi (n=54). ORR was 18.5% [8.2- 28.9%] with Nivo, and 27.8% [15.8-39.7%] with Nivo+Ipi. Grade 3/4 toxicities were slightly increased in the combo arm (Nivo: 12.7%/0% vs. Nivo+Ipi: 22.9%/3.3%) with 3 treatment-related deaths in the combo arm. Median follow-up was15 months (July, 31th 2017), median PFS was 4.0 months, 95%CI[2.8-5.7] and 5.6 months 95%CI[3.2- 8.4] in Nivo and Nivo+Ipi arms, respectively. Median OS was 13.6 months, 95%CI[6.7-NR] and not reached in Nivo and Nivo+Ipi arms, respectively. 12-months OS were 51% and 58% in Nivo and Nivo+Ipi arms respectively. PD-L1 IHC (mAb 28.8) available in 99/125 patients, was positive (>1% PDL1+ tumor cells) in 41.4%. Positive PD-L1 IHC did not predict longer PFS or OS, either in the whole population or in each treatment group separately. Conclusions: Both Nivo or Nivo+Ipi reached their endpoint in 2nd/3rd lineMPM pts without any unexpected toxicity, leading to meaningful progression-free and overall survivals. These updated results support the efficacy of checkpoints inhibitors inMPM patients, deserving future phase 3 trials.