atezolizumab plus bevacizumab (n=336) vs. sorafenib (n=165)
randomized controlled trial
atezolizumab-bevacizumab
atezolizumab–bevacizumab group received 1200 mg of atezolizumab plus 15 mg per kilogram of body weight of bevacizumab intravenously every 3 weeks
sorafenib
400 mg of sorafenib orally twice daily
Dose modifications were not permitted in the atezolizumab–bevacizumab group but were allowed in the sorafenib group.
mHCC - 1st line (L1)
open design
111 sites in 17 countries
P3/two sided One analysis of PFS, two interim analyses, and a final analysis of OS. Repartition, reallocation and hierarchy OS PFS and ORR (arm A then arm B)
In patients with unresectable hepatocellular carcinoma, atezolizumab combined with bevacizumab resulted in better overall and progressionÂfree survival outcomes than sorafenib
CheckMate 459, 2019 NCT02576509
nivolumab alone (n=371) vs. sorafenib (n=372)
randomized controlled trial
nivolumab
NIVO 240 mg IV Q2W
sorafenib
Sorafenib (400 mg oral BID).
mHCC - 1st line (L1)
open label
at medical centres in 22 countries and territories in Asia, Australasia, Europe, and North America
P3 / OS at 2-sided at 0.05 with one IA (at 0.024) and one final analysis (at 0.043). Hierarchical testing: OS > ORR > PFS
this study did not meet its primary endpoint OS
LEAP 002, 0 NCT03713593
pembrolizumab plus lenvatinib (n=-9) vs. lenvatinib (n=-9)
randomized controlled trial
lenvatinib in combination with pembrolizumab
Lenvatinib
mHCC - 1st line (L1)
study Misses Primary End Points
ORIENT-32, 2021 NCT03794440
sintilimab (n=380) vs. sorafenib (n=191)
randomized controlled trial
Sintilimab plus IBI305 (bevaciumab biosimilar)
200mg of sintilimab intravenously over 60min, followed by 15mg/kg body weight of IBI305 bevacizumab biosimilar intravenously over 90min (the second infusion over 60min, and afterwards over 30min if no infusion reaction occurred), every 3 weeks
Sorafenib
400mg orally twice a day
mHCC - 1st line (L1)
open label
China
P3 / two sided alpha = 0.05. First test of PFS at alpha = 0.002, if PFS is statistically significant, the test of the OS would be at alpha = 0.05. If PFS is not statistically significant, the test of the OS would be done with alpha at 0.048.