Benzinga | Jan 21, 2022 10:02AM EST

Mirati Therapeutics Highlights Presentation Of Data With Adagrasib In Patients With KRASG12C-Mutated Gastrointestinal Cancers

Mirati Therapeutics, Inc. (NASDAQ:MRTX), a clinical-stage targeted oncology company, today 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. The findings (Abstract # 519) will be presented today at 10:00 a.m. ET during a rapid abstract session at the 2022 American Society for Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium.

Dr. Tanios S. Bekaii-Saab, an investigator of the KRYSTAL-1 study, commented, "Gastrointestinal cancers are some of the most common cancers and continue to be associated with poor survival outcomes despite recent advances, especially in patients with GI tumors harboring a KRASG12C mutation. New clinical data presented at ASCO GI show that adagrasib, an inhibitor of KRASG12C, demonstrated promising clinical activity in patients with pancreatic cancer and other GI tumors. These findings build on the previously reported positive adagrasib clinical data in colorectal and pancreatic cancers, and are highly encouraging, warranting further investigation of adagrasib in this setting."

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.

"We believe adagrasib has a differentiated molecular profile, and the data presented at ASCO GI further support its potential best-in-class profile," said Charles M. Baum, M.D., Ph.D., founder, president and head of research and development, Mirati Therapeutics, Inc. "The results demonstrated positive clinical activity in patients with KRASG12C-mutated GI cancers treated with single agent adagrasib, particularly in those with pancreatic cancer where options are limited. We continue to aggressively evaluate adagrasib as a single agent and in combination with other cancer medicines in a broad development plan to help more people living with cancer."