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

      Background: No treatment is currently recommended in MPM pts 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 proved MPM 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 line MPM pts without any unexpected toxicity, leading to meaningful progression-free and overall survivals. These updated results support the efficacy of checkpoints inhibitors in MPM patients, deserving future phase 3 trials.
      Clinical trial identification: NCT02716272
      Legal entity responsible for the study: Intergroupe Francophone de Cancérologie Thoracique (IFCT)
      Funding: BMS
      Disclosure: G. Zalcman: Advisory board for MSD, Boehringer-Ingelheim, BMS Grants and personal fees from BMS, Roche, Astra-Zeneca, Novartis. Compensation for meeting attendance and accommodation: Roche, Astra-Zeneca, BMS, Pfizer. J. Mazieres: Research funding from BMS & Roche. L. Greillier: Honoraria from Boehringer-Ingelheim, BMS, Lilly, Pfizer, Astra-Zeneca, Novartis, Roche. Avisory role for Borhingher-Ingelheim, BMS, Roche. Research funding for my institution from Roche. Travel and accommodation from Lilly, Pfizer, Boehringer-Ingelheim. I. Monnet: Research funding from MSD, Astellas Oncology, Astra-Zeneca. Travel & accommodation from MSD, Novartis. R. Corre: Advisory role for Roche, Lilly, BMS, Astra-Zeneca. Travel & accommodations from Boerhinger-Ingelheim, Amgen, Roche. Honoraria from Boerhinger-Ingelheim. C. Audigier-Valette: Advisory role: Roche, Pfizer, Boerhinger, Novartis, Astra-Zeneca, Lilly, Amgen, BMS, Sysmex, MSD, Clovis Oncology, Medimmune. Travel/accommodations from Roche, Pfizer, Lilly, Amgen, Novartis, BMS, MSD, Medimmune. M. Locatelli-Sanchez: Travel & accommodation from Pierre Fabre and Boerhinger-Ingelheim. O. Molinier: Advisory role for BMS, Boerhinger-Ingelheim, Astra-Zeneca, Novartis, Roche. D. Planchard: Avisory Role for Lilly, BMS, Pfizer, Clovis oncology, MSD, Sanofi, Astra-Zeneca, Novartis, Roche. Research funding from Novartis. D. Moro-Sibilot: Honoraria from La Lettre du Cancérologue, Roche, BMS, Pfizer, Boerhinger, Lilly, Astra-Zeneca. Travel and accommodation from Roche. A. Scherpereel: Invitations at international meetings (ASCO, iMig, CPLF, AACR): Roche, MSD, BMS, France Oxygene. Honoraria for participation to scientific or advisory boards, organized by Astra-Zeneca, BMS, Boehringer-Ingelheim, MSD, Roche. All other authors have declared no conflicts of interest.