Adagrasib Shows High Response Rates in GI Cancers

Tanios S. Bekaii-Saab, MD, FACP, medical oncologist, medical director, Cancer Clinical Research Office, vice chair and section chief, Medical Oncology, Department of Internal Medicine, Mayo Clinic, discusses data from the phase 1/1b and 2 KRYSTAL-1 trial (NCT03785249), which he presented during the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

The phase 2 cohort in this study reviewed dose escalation of adagrasib (MRTX 849) to determine the maximum tolerated dose to be 600 mg twice a day. Adagrasib showed promising clinical activity in previously treated patients with advanced or metastatic solid tumors who had a KRAS G12C mutation throughout each of the phases.

The study basket included 42 patients, however, Saab presented on the 30 patients with gastrointestinal (GI) tumors other than colon cancer, primarily pancreas cancer, and biliary cancer. These patients had a poor performance status and for the most part, treated with 2 or more lines of therapies.

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0:08 | What was interesting is that when we looked at the response rate with pancreas cancer, it was 50% in the cohort of patients that was evaluable for response, and there was 100% disease control rate, meaning none of these patients had progression at the time of analysis. For the other GI cancers, there was 35% for the response rate, and 100% for the disease control rate. Across all the GI malignancies, there were essentially no patients who progressed and about 40% plus of the patients had a response. When you look at the pancreas, the median immediate progression free survival was 6.6 months and the patients continued on treatment with the other GI tumors, the median PFS was almost 7.9 months, and about 2/3 of the patients continued on treatment.

1:08 | When you look at the other GI cancers, the majority were actually biliary tract cancer, cholangiocarcinoma, and again, there were about half of the patients who had actual responses. Interestingly, this is a relatively well tolerated agent. Most of the toxicities were grade 1 and 2, there were no grade 4 or 5. The ones that were grade 3 were primarily fatigue QT prolongation but none of them actually led to discontinuation.