Mirati Therapeutics, Inc. announced positive results from a Phase 2 cohort of the KRYSTAL-1 study evaluating adagrasib at the 600mg BID dose in patients with pretreated pancreatic ductal adenocarcinoma and other gastrointestinal (GI) tumors harboring a KRASG12C mutation, including cancers of the biliary tract, appendix, small bowel, gastro-esophageal junction, and esophagus. Results showed that adagrasib demonstrated significant clinical activity and broad disease control. Summary of Clinical Results: As of September 10, 2021, the subset of patients with GI cancers harboring a KRASG12C mutation enrolled in the adagrasib monotherapy arm (n=30) received at least two prior lines of systemic anticancer therapies, and had a median follow up of 6.3 months.

Of the evaluable patients (n=27), the objective response rate (ORR) was 41% and the disease control rate (DCR) was 100%. In evaluable patients with pancreatic cancer (n=10), the response rate (RR) was 50%, including 1 unconfirmed partial response (PR); the median duration of response (mDOR) was 7.0 months, with a median follow up of 8.1 months. In patients with other GI tumors (n=17), the RR was 35%, with two unconfirmed PRs; the mDOR was 7.9 months in these patients, with a median follow up of 6.3 months.

The median progression free survival (mPFS) in patients with pancreatic cancer was 6.6 months (95% Confidence Interval, CI: 1.0, 9.7), and in patients with the other GI tumors, the mPFS was 7.9 months (95% CI 6.90–11.30). In the overall subset of patients with KRASG12C-mutated GI cancers evaluated in this cohort, adagrasib was well-tolerated, with a manageable safety profile. Grade 3/4 treatment-related adverse events (TRAEs) were observed in 27% of patients treated with adagrasib, with no TRAEs leading to treatment discontinuation, and no Grade 5 TRAEs observed.