Second- or third-line nivolumab (Nivo) versus nivo plus ipilimumab (Ipi) in malignant pleural mesothelioma (MPM) patients: Results of the IFCT-1501 MAPS2 randomized phase II trial.

Abstract

LBA8507 Background: To date, no treatment is recommended in MPM pts progressing after 1st-line pemetrexed-platinum doublet. Disease control rate (DCR) is <30% with all drugs tested in 2nd-line setting. Preliminary results suggested possible activity of anti-PD-1 mAb in 2nd/3rd-line, opposed to single agent anti-CTLA-4 mAb. Therefore anti-PD1 mAb efficacy deserves confirmation, and anti-PD-1 + anti-CTLA-4 combination value is currently unknown in MPM. Methods: In this multicenter randomized non comparative phase 2 trial, eligible pts had age>18, PS 0-1, histologically proven 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 + Ipi 1 mg/kg q6w, until progression or unacceptable toxicity. Primary endpoint was DCR at 12 weeks with a blinded independent central review (BICR). 114 patients were to be randomized (with 108 eligible), with one-step Fleming procedure, H0 P<20% vs H1 P>40%, with 95% power, 5% one-sided a-risk: ≥17 failure-free pts had to be observed at 12 weeks in either arm, to conclude to the activity of the corresponding regimen. Results: From March to August 2016, 125 pts were enrolled in 21 centers. Males: 80%, median age: 71.8 years (range 32.5-88.1), PS 1: 62.4%, epithelioid 83.2%, 1 previous line: 69.6%; 70% of pts received ≥ 3 cycles of either treatment. Twelve weeks-DCR assessed by BICR in the first 108 eligible pts was 42.6% [IC95%: 29.4-55.8%] with Nivo (n=23/54), and 51.9% [38.5-65.2%] with Nivo+Ipi (n=28/54). ORR was 16.7% [6.7%-26.6%] with Nivo (n=9/54), and 25.9% [14.2-37.6%] with Nivo+Ipi (n=14/54). All grade/G3-4 toxicities were slightly increased in the combo arm (86.9%/16.4%) vs Nivo alone (77.8%/9.5%); 3 treatment-related deaths were observed in the combo arm (1 metabolic encephalopathy, 1 fulminant hepatitis, 1 acute renal failure). Full QoL, PFS and OS data will be presented at 2017 ASCO meeting. Conclusions: Both Nivo and Nivo+Ipi arms reached their endpoint in 2nd/3rd-line MPM pts, suggesting that immunotherapy may provide new options for these pts. Clinical trial information: NCT02716272.