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ASCO 2022 | CodeBreak100: assessing sotorasib in patients with KRAS p.G12C-mutant pancreatic cancer

KRAS mutations are present in 90% of pancreatic ductal adenocarcinomas (PDACs). P.G12C accounts for 1-2% of these KRAS mutations. John H. Strickler, MD, Duke Cancer Institute, Durham, NC, provides an overview of the international, single-arm, Phase I/II trial, CodeBreak100 (NCT03600883) exploring the KRAS p.G12C inhibitor, sotorasib, in patients with previosuly treated pancreatic cancer harboring the KRAS p.G12C mutation. The primary endpoint is confirmed objective response rate (ORR) and secondary endpoints include duration of response (DoR), progression-free survival (PFS) and overall-survival (OS). 38 patients with pancreatic cancer received sotorasib once daily. ORR was 21.1% and DCR was 84.2%, with a PFS of 4 months and median DoR of 6 months. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.

Transcript (edited for clarity)

Patients with pancreatic cancer often face a poor prognosis and limited treatment options. And unfortunately, until now we’ve not had an effective way to target KRAS, which is found in 90% of pancreatic cancers. The molecule that’s under study here, sotorasib, targets specifically KRAS12C which is found in one to 2% of patients with pancreatic cancer. Already, this molecule has found itself to be highly active in non small cell lung cancer, and also has shown activity in colorectal cancer...

Patients with pancreatic cancer often face a poor prognosis and limited treatment options. And unfortunately, until now we’ve not had an effective way to target KRAS, which is found in 90% of pancreatic cancers. The molecule that’s under study here, sotorasib, targets specifically KRAS12C which is found in one to 2% of patients with pancreatic cancer. Already, this molecule has found itself to be highly active in non small cell lung cancer, and also has shown activity in colorectal cancer. So in this ASCO plenary series update that was presented here at the conference, we showed that this molecule had a 21% response rate in pancreatic cancer with a four month progression free survival, which in the context of the current treatment landscape is very favorable. Additionally, it appears that the progression free survival is meaningful at four months and the median duration of response was nearly six months. So it appears that in this difficult to treat disease, there’s a therapy that has some activity. It’s very promising for future study.

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