CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 NCT02477826
nivolumab plus ipilimumab (n=139) vs. pemetrexed plus platin (n=160)
randomized controlled trial
nivolumab plus ipilimumab
nivolumab (3 mg per kilogram of body weight every 2 weeks) plus ipilimumab (1 mg per kilogram every 6 weeks)
platinium chemotherapy
platinum doublet chemotherapy based on tumor histologic type every 3 weeks for up to four cycles : pemetrexed (500 mg per square meter of body-surface area) plus cisplatin (75 mg per square meter) or carboplatin (area under the concentration-time curve [AUC], 5 or 6), every3 weeks for up to four cycles
3 arms: Nivolumab, or Nivolumab Plus Ipilimumab. Crossover between treatment groups within the trial was not permitted.
mNSCLC - L1 - TMB>10Mb
Patients with known EGFR mutations or ALK translocations sensitive to targeted therapy, an autoimmune disease, or untreated central nervous system metastases were excluded.Tumor mutational burden was determined by the FoundationOne CDx assay,
open label
NA
P3/ two sided and one interim analysis. Repartition between coprimary end point and hierarchy with secondary endpoint.
Progression-free survival was significantly longer with first-line nivolumab plus ipilimumab than with chemotherapy among patients with NSCLC and a high tumor mutational burden, irrespective of PD-L1 expression level