pembrolizumab plus SoC (n=373) vs. placebo plus SoC (n=376)
randomized controlled trial
Pembrolizumab with cisplatin and 5 FU :
Pembrolizumab at 200 mg on day 1 of each 3-week cycle, for up to 35 cycles Cisplatin in both study arms is administered at a dose level of 50 mg/m2 on day 1 of each 3-week cycle for up to 6 cycles, and 5-FU was administered at 800 mg/m2 per day on day 1 to day 5 of each 3-week cycle for up to 35 cycles
placebo with cisplatin and 5 FU :
Cisplatin in both study arms is administered at a dose level of 50 mg/m2 on day 1 of each 3-week cycle for up to 6 cycles, and 5-FU was administered at 800 mg/m2 per day on day 1 to day 5 of each 3-week cycle for up to 35 cycles
mEC - 1st line (L1)
double-blind
across 168 medical centres in 26 countries
P3 / 1 IA and 1 final analysis: the 1st IA (= the final analysis of PFS) was planned after at least 13mo of follow-up. Overall type I error at a 1-sided at 0.25 with 0.12 to OS in patients with PD-L1> 10, 0.11 to ITT patients and 0.02 to PFS in ITT patients. Re-allocation of overall type I error to other outcomes according to graphical method p13 of the appendix
KEYNOTE-181, 2020 NCT02564263
pembrolizumab alone (n=314) vs. Standard of Care (SoC) (n=314)
randomized controlled trial
Pembrolizumab
pembrolizumab 200 mg Q3W for up to 2 years
chemotherapy ICC (paclitaxel, docetaxel, or irinotecan)
investigator’s choice chemo of paclitaxel, docetaxel, or irinotecan.paclitaxel 80-100 mg/m on days 1, 8, and 15 Q4W, docetaxel 75 mg/m Q3W, or irinotecan 180 mg/m Q2W.