Dr Pant on the Investigation of Adagrasib in KRAS G12C–Mutated Solid Tumors

Shubham Pant, MD, MBBS, associate professor, departments of Investigational Cancer Therapeutics and Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the investigation of adagrasib (Krazati) in the treatment of patients with KRAS G12C–mutated advanced solid tumors.

At the 2023 ASCO Annual Meeting, Pant presented updated data from the ongoing phase 1/2 KRYSTAL-1 trial (NCT03785249), which is evaluating the activity and safety of the covalent KRAS G12C inhibitor, adagrasib, in patients with advanced solid tumors harboring KRAS G12C mutations. Patients with non–small cell lung cancer (NSCLC) or colorectal cancer (CRC) were not included in this phase 2 cohort.

In 57 evaluable patients, the confirmed objective response rate (ORR) was 35.1%, with all responders achieving a partial response. Additionally, 50.9% of patients had stable disease, leading to a disease Control rate of 86.0%.

Specifically in the cohort of patients with pancreatic ductal adenocarcinoma (n = 21), the ORR was 33.3% with a disease control rate of 81.0%. Patients with biliary tract cancer (n = 12) experienced an ORR of 41.7% and a disease control rate of 91.7%.

In December 2022, the FDA granted accelerated approval to adagrasib for the treatment of adult patients with KRAS G12C–mutated locally advanced or metastatic NSCLC who have received at least 1 prior systemic therapy.

The goal of this phase 2 cohort was to further evaluate the KRAS G12C inhibitor given as a single agent in patients with advanced solid tumors other than NSCLC and CRC, Pant expands. This portion of the study included patients with pancreatic cancer, endometrial cancer, ovarian cancer, and biliary tract cancer, where only a small portion of patients harbor KRAS G12C mutations, Pant explains. Adagrasib was dosed at 600 mg twice per day, mirroring the portion of the study that supported the FDA accelerated approval in NSCLC.