Gastric Cancer: Frontline Checkpoint Inhibitor Trials

Kei Muro, MD: In the first-line setting using PD-1 or PD-L1 antibodies, CheckMate649 (NCT02872116) is a very attractive regimen because the population is more than 2000 patients. It’s a very huge randomized controlled trial. In addition, nivolumab and ipilimumab as an IO/IO combined regimen is very promising for me. It is a huge randomized controlled trial, but the primary end point is very simple and the α was limited. As you know, the KEYNOTE-062 trial (NCT02494583) has many primary end points and the α was divided. The primary end point was with very limited data. Given noninferiority in overall survival with pembrolizumab monotherapy versus chemotherapy, the frontline standard of care was established. However, CheckMate649 is huge and has very limited α. That’s very promising to show the benefit of overall survival.

Second is ATTRACTION-4 (NCT02746796). It’s mainly Asian countries’ data with doublet chemotherapy plus nivolumab or nivolumab plus doublet placebo. This trial is also very promising, with limited α and more than 600—around 680—patients involved. At the end of this year, it will be open in overall survival data.

Another promising first-line treatment is the KEYNOTE-811 trial (NCT03615326). These are patients who are HER2-positive gastric cancer being treated with a doublet plus trastuzumab plus pembrolizumab therapy compared with standard of care doublet plus trastuzumab therapy. An already opened trial, a single-arm phase 2 trial from Memorial Sloan Kettering Cancer Center, showed very good data and an overall response rate of more than 70%. Good data are shown in that phase 2 trial, and we hope there will be phase 3 positive data in KEYNOTE-811.

Transcript edited for clarity.