Dr. Bekaii-Saab on the Updated Results of the KRYSTAL-1 Trial in KRAS G12C+ GI Cancers

Tanios S. Bekaii-Saab, MD, FACP, professor of medicine, consultant, medical oncologist, leader, Gastrointestinal Cancer Program, medical director, Cancer Clinical Research Office, vice chair and section chief, Medical Oncology, Department of Internal Medicine, Mayo Clinic, discusses the updated results of the ongoing phase 1/2 KRYSTAL-1 trial (NCT03785249) in KRAS G12C-mutated gastrointestinal (GI) cancers, including pancreatic ductal adenocarcinoma (PDAC).

The KRYSTAL-1 trial is evaluating the activity and safety of adagrasib in patients with unresectable or metastatic, KRAS G12C-mutated, PDAC and other GI tumors. Updated results from the study, which were presented during the 2022 Gastrointestinal Cancers Symposium, demonstrated promising clinical activity and a 100% disease control rate in patients with previously treated, KRAS G12C-mutated PDAC and other GI cancers.

The response rate was 50% in patients with PDAC and 50% in patients with biliary tract cancer, Bekaii-Saab says. The median progression-free survival was 6.6 months in patients with PDAC and 7.85 months for patients with other GI cancers. The median duration of response was 6.97 months and 7.85 months, respectively. Moreover, 50% and 65% of patients, respectively, remain on treatment.

The toxicities associated with adagrasib were manageable and were comprised primarily of GI toxicities. No grade 4 or 5 toxicities were observed, and no treatment-related events led to treatment discontinuation. The most common grade 3 adverse effects beyond GI events included fatigue, aspartate transaminase increase, blood creatinine increase, anemia, peripheral edema, QT prolongation, alanine transaminase increase, and dysgeusia, Bekaii-Saab concludes.