KRYSTAL-1: adagrasib in advanced solid tumours harbouring a KRAS G12C mutation, including pancreatic cancer
Adagrasib, the second KRAS G12C pill, shrank tumours in about a third of patients with pancreatic cancer and in two in five with bile duct cancer in this basket study, with disease control for several months.
Overview
Phase 2 cohort of the KRYSTAL-1 trial in 64 patients with previously treated KRAS G12C-mutated solid tumours other than lung or colorectal cancer, treated with adagrasib 600 mg twice daily. The pancreatic cohort had 21 patients and the biliary tract cohort 12; other tumours included appendiceal, ovarian, endometrial and small bowel cancers.
In pancreatic cancer the objective response rate was about 33 percent, with median progression-free survival of 5.4 months and median overall survival of 8.0 months; in biliary tract cancer the response rate was about 42 percent. Treatment-related adverse events were mostly gastrointestinal and manageable with dose reduction.
- Pancreatic cohort (21 patients): objective response about 33 percent, median progression-free survival 5.4 months, median overall survival 8.0 months.
- Biliary tract cohort (12 patients): objective response about 42 percent.
Adagrasib joins sotorasib as a later-line option for KRAS G12C pancreatic cancer in guidelines; both drugs are the template for the G12D and pan-RAS inhibitors now in pancreatic trials.
- Small single-arm cohorts with a short follow-up; the pancreatic response rate has a wide confidence interval.
- KRAS G12C is found in only 1 to 2 percent of pancreatic cancers.
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