Evolution of Agents Targeting KRAS G12C Mutated Gastrointestinal Cancers

Tanios S. Bekaii-Saab, MD, FACP, medical oncologist, medical director, Cancer Clinical Research Office, vice chair and section chief, Medical Oncology, Department of Internal Medicine, Mayo Clinic, discusses the evolution of treatment options prior to adagrasib (MRTX849) for patients with KRAS G12C mutations.

While there are now many developments to help manage patients with KRAS G12C mutations, they are on the newer side and the space is still growing. Previously, experts only had access to a few agents which indirectly affected the mitogen-activated protein kinase (MAPK) pathway downstream.

Ongoing research now aims to examine sotorasib (Lumakras) and adagrasib, some of the first agents in this space. According to Bekaii-Saab, sotograsib is mostly being examined in lung cancer and other cancers expressing G12C, while adagrasib is being looked at in various malignancies, including gastrointestinal cancers.

Transcription:

0:08 | The whole area of targeting KRAS is recent. For the longest time, there were no agents. We only had some agents that indirectly may affect the mitogen-activated protein kinase pathway downstream, such as MEK inhibitors and developing drug inhibitors and others. The 2 agents that made it to first being tested, targeting KRAS, specifically KRAS G12C, are sotorasib and adagrasib. Those are very specific to KRAS G12C.

0:54 | Sotograsib and adagrasib were developed in parallel by 2 different companies, but more are being developed right now in the same space by others. This area is becoming very active for a specific agent. Sotograsib is in lung cancer and being tested in a variety of different cancers expressing G12C, from GI to ovarian. The same with adagrasib which is being developed in various malignancies, most advanced moving into lung and colorectal. The data I presented is in other GI malignancies.