Sotorasib, an irreversible inhibitor of KRAS G12C, showed activity in patients with metastatic pancreatic cancer and a KRAS G21C mutation enrolled in the phase I/II CodeBreaK100 study. These findings were presented during the February 2022 ASCO Plenary Series session by John H. Strickler, MD, Associate Professor of Medicine at Duke University Medical Center (Abstract 360490).
John H. Strickler, MD
Treatment with sotorasib was associated with a centrally confirmed objective response rate of 21.1% and a disease control rate of 84.3% in heavily pretreated patients, demonstrating “clinically meaningful activity” in the largest data set yet to evaluate the efficacy and safety of a KRAS G12C inhibitor in pancreatic cancer, Dr. Strickler said.
Invited discussant E. Gabriela Chiorean, MD, of the University of Washington and Fred Hutchinson Cancer Center Research Center, Seattle, found the efficacy “remarkable” in the third or later treatment line. She added, “These data are a stepping stone for future combinatorial approaches with sotorasib.”
Sotorasib is an irreversible KRAS G12C inhibitor that has been approved by the U.S. Food and Drug Administration for the treatment of patients with non–small cell lung cancer and KRAS G12C mutations. While KRAS mutations are almost ubiquitous in metastatic pancreatic cancer, only 1% to 2% are KRAS G12C mutations. Currently, this subset of patients has no approved targeted therapy, and their survival after disease progression on two regimens is usually less than 6 months, Dr. Strickler noted.
About CodeBreak100
CodeBreaK100 is an international, single-arm, phase I/II study evaluating the efficacy and safety of sotorasib in patients with advanced solid tumors and a KRAS G12C mutation. The population included 38 patients with stage IV pancreatic cancer treated with at least one prior systemic therapy or not eligible for or able to tolerate available therapies.
More than half the patients had de novo stage IV disease at diagnosis, and 79% had received at least two prior lines of therapy. Patients were treated with oral sotorasib at 960 mg daily. The primary efficacy endpoint was confirmed objective response rate.
Median treatment duration was 4.1 months and median follow-up was 16.8 months. By blinded central review of the intent-to-treat population, partial responses were confirmed in 21.1%, and 84.2% of patients attained disease control; median duration of response was 5.7 months.
Of the 38 patients, 30 had a reduction in the sum of their lesions over baseline, and 2 patients had ongoing responses at data cutoff. Median progression-free survival was 4.0 months, and median overall survival was 6.9 months.
Sotorasib was well tolerated, with most adverse events being grade 1 or 2 and manageable. None were fatal or led to discontinuation of the drug, Dr. Strickler said.
“These data are promising for patients with pancreatic cancer and high unmet medical needs who have limited treatment options,” Dr. Strickler said.
Disclosure: For full disclosures of the study authors, visit coi.ascopubs.org.
