KRAS is a cancer gene has been studied for about 40 years, reports Memorial Sloan Kettering Cancer Center (MSKCC). It is known to be associated with a number of cancers such as about 25% of lung cancers and between 33% and 50% of colon and rectal cancers. Until recently it was considered an “undruggable” target, but that’s changing as researchers develop targeted therapies to actually block the activities of these types of genes that are associated with cancer. Now investigators from MSKCC and other prominent centers report positive signals from the CodeBreak 100 clinical trial, investigating sotorasib, called AMG 510 by Amgen. The results are promising but not a “home run.” There is much work to do to cure cancer.
The results from the CodeBreak 100 clinical trial were recently published in New England Journal of Medicine (NEJM).
The CodeBreak 100 Trial
Sponsored by Amgen, the CodeBreak 100 study (NCT03600883) commenced back in August of 2018. Recently investigators reported results from this first-ever clinical investigation of a drug that directly targets KRAS. The multicenter study targeted 533 participants.
In this international based clinical trial investigators discovered that a drug known as sotorasib (AMG 510) slowed or stopped cancer growth in a number of participants with advanced cancer that also happened to have the KRAS mutation. Of course, more needs to be understood but this is a significant first step writes Julie Grisham for Memorial Sloan Kettering Cancer Center (MSKCC).
The sponsor ultimately enrolled 129 patients whose tumors had KRAS-G12C. 59 of the patients had non-small cell lung cancer, 42 colorectal cancer and 28 other types of tumors reports Ms. Grisham. The patients all had experienced the cancer spread around the body and had already been exposed to multiple treatments. These trial participants had been treated in hospitals from around the world.
Of the 59 lung cancer patients, 7 patients didn’t respond and 52 experienced disease control (the tumors stopped growing or even shrank). Among the 52 patients, 19 of the patients experienced a substantial shrinkage of tumor. The average duration for worsening of the disease was 6 months. this
Principal Investigator Point of View
Memorial Sloan Kettering medical oncologist Bob Li, senior investigator and corresponding author commented, “Sotorasib is not a cure, but this study is the first to crack KRAS in a clinically meaningful way.” Dr. Li continued, “It’s an important step forward, but it’s not yet a home run.”
Sotorasib (AMG 510) is an experimental cancer drug. It targets a specific mutation, G12C, in the protein KRAS which is responsible for various forms of cancer. As described in the NCI, its an orally available agent that targets this above mutation with potential antineoplastic activity. Upon oral administration, the drug selectively targets the KRAS p.G12C mutant, at either the DNA, RNA or protein level, and stops, via a still to be determined manner, expression of an/or tumor cell signaling via the KRAS p.G12C mutant. In this way, this investigational drug can inhibit growth in KRAS p.G12C expressing tumor cells.
The CodeBeak 100 study was sponsored by Amgen but also received support from a number of other institutions including Cancer Prevention Research Institute of Texas (CPRIT) Precision Oncology Decision Support Core Grant, Memorial Sloan Kettering Cancer Center from the National Institutes of Health, and others.
Other authors can be viewed here.
Call to Action: Follow the link to read Ms. Grisham’s entire, well-written account.