The ASCO Post invited Mandana Kamgar, MD, MPH, Assistant Professor of Medicine at the Medical College of Wisconsin, LaBahn Pancreatic Cancer Program, Milwaukee, to comment on the KRYSTAL-1 trial.

“The KRYSTAL-1 study in totality is a multiphase and multiarm ongoing study exploring the role of adagrasib (MRTX849), an irreversible covalent inhibitor of KRAS G12C, in multiple tumors, including lung, colorectal, and other solid tumors with the KRAS G12C mutation. The presentation by Dr. Bekaii-Saab during the rapid abstract session was a subset study of the solid tumor arm in the phase II portion, focusing on the 30 patients with noncolorectal gastrointestinal malignancies. This is a preliminary report at a median follow-up of 8.1 months on the activity and safety of adagrasib at 600 mg twice daily. The most represented gastrointestinal malignancies in this arm were pancreatic (n = 12) and biliary tract cancers (n = 8),” she noted.

Dr. Kamgar continued: “Focusing on the pancreatic group, among the 10 patients with evaluable disease, the reported 50% partial response and 100% disease control rates were encouraging. Furthermore, the median progression-free survival of 6.6 months (95% confidence interval = 1.0–9.7 months) with treatment ongoing in 5 of 10 patients is promising.”

“Considering the acceptable safety profile, this brings hope for the rare subset of pancreatic adenocarcinoma with KRAS G12C mutations. It is yet to be determined how long these responses last, and how tumors develop resistance to this treatment, but if the promising results hold at the time of data maturity, adagrasib might offer a new option for advanced gastrointestinal malignancies with KRAS G12C mutations,” concluded Dr. Kamgar. The optimal sequencing of this treatment with cytotoxic chemotherapy merits prospective evaluation, she added. 

DISCLOSURE: Dr. Kamgar reported no conflicts of interest.