Sotorasib

Staying with lung cancer, Roche ran a direct contest.

Its Crescendo 1 trial tested Divaracib, an investigational KRAS G12C drug, against the drugs already available in that class, Sotoracib or Adagracib, whichever the investigator chose.

The trial enrolled 338 previously treated patients with advanced KRASG12C-positive non-small-cell lung cancer.

Median progression-free survival was 9.8 months with divaricib versus 5.7. Interim overall survival was 17.7 months versus 12.0.

That's despite patients staying on divaricib longer, a median of 11.3 months versus 5.0.

The trial was open-label, so those are descriptive comparisons.

Divaricib has now been measured against the class it's trying to enter.

It held up on progression and interim survival, and the discontinuation numbers point the same way.

A series of structural biology breakthroughs revealed that KRAS G12C mutation creates a small cysteine residue that could be covalently targeted, essentially allowing a molecule to form a permanent chemical bond with the mutant protein and locking it in the inactive state.

Amgen's Sotorasib, which received FDA approval in 2021, was the first KRAS G12C inhibitor, which proved that the concept is real.

The undruggable target could be drugged, at least in one mutation site.

But KRAS G12C is only one piece of the RAS problem, right? G12D is more common in pancreatic cancer, and pancreatic cancer, by the way, is definitely the harder to treat cancers along with the brain cancer.