In light of the 2024 Shkreli Awards, how do you address patient concerns regarding the 240 mg versus 960 mg dose of sotorasib?

The randomized dose comparison study of sotorasib 960 mg versus 240 mg was conducted as part of an initiative from the US FDA Project Optimus, based on observations in the early phase dose-escalation study demonstrating non-dose proportional increases in drug exposure at dose levels of about 180 mg once daily along with clinical responses seen across dose levels.

The primary endpoint of ORR was numerically higher in the 960 mg versus 240 mg group (33% vs 25%). Disease control rate is also numerically higher (87% vs 82%). PFS curves were overlapping whereas OS was also numerically higher with the higher dose (13 vs 11.7 months) but this may be impacted by variance in post-study exposure to subsequent therapy. Moreover, the higher dose also h...