Data from the phase 1/2 CodeBreaK 100 trial indicated that 84% of patients with KRAS G12C-mutated pancreatic cancer treated with sotorasib experienced disease control.
Treatment with sotorasib (Lumakras) demonstrated meaningful clinical activity among heavily pretreated patients with metastatic pancreatic cancer harboring KRAS G12C mutations, according to a study results from the phase 1/2 CodeBreaK 100 trial (NCT03600883).1
Investigators observed an objective response rate (ORR) of 21.1% and a median time-to-response of 1.5 months among patients receiving sotorasib. Additionally, 84% of patients experienced disease control, and the median progression-free survival (PFS) and overall survival (OS) rates, respectively, were 4 months and 6.9 months.
“These are encouraging early data because they point toward establishing that KRAS inhibitors can work in pancreatic cancers, which have been difficult to crack from a targeted therapy standpoint,” lead trial investigator David S. Hong, MD, professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, said in a press release.2 “We look forward to data from larger trials as we continue working to bring much-needed new therapies to these patients.”
Primary end points of the CodeBreaK trial included the incidence of treatment-emergent adverse events (TEAEs), treatment-related AEs (TRAEs), dose-limiting toxicities, ORR, duration of response, disease control, duration of stable disease, and time to response.
Secondary end points included the plasma concentration of sotorasib, PFS, OS, and health-related quality of life as assessed by surveys including the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire.
Patients 18 years and older with a pathologically documented, locally advanced or metastatic malignancy harboring KRAS G12C mutations identified through molecular testing were eligible to enroll on the trial. Patients with active brain metastases from non-brain tumors, myocardial infarction, or a gastrointestinal tract disease interfering with the ability to take oral medication were unable to enroll.
The pancreatic cancer cohort of the CodeBreaK 100 trial included 38 patients (median age, 65.5 years) with metastatic disease who received a median of 2 prior lines of therapy. Most (76.3%) of the patients were men, and 55.3% had stage IV disease at baseline.
TEAEs were observed in all patients during the trial, the most frequent of which included abdominal pain (36.8%), diarrhea (23.7%), and nausea (23.7%). A total of 42.1% of patients had TRAEs, with 15.8% of events being grade 3. Additionally, no patients discontinued treatment due to AEs.
Previously, the FDA granted accelerated approval to sotorasib for the treatment of patients with KRAS G12C-mutated non–small cell lung cancer in May 2021.3 The approval was based on data from the CodeBreaK 100 trial, in which treatment with sotorasib yielded an ORR of 36% (95% CI, 28%-45%) among patients with locally advanced or metastatic disease progressing after use of immune checkpoint inhibitors or platinum-based chemotherapy.
The study investigators noted the significance of these findings.
“Sotorasib monotherapy showed promising anticancer activity in patients with heavily pretreated KRAS p.G12C–mutated advanced pancreatic cancer,” they wrote. “The clinical activity of sotorasib shown in this trial provides evidence that targeting KRAS is a viable strategy for the treatment of advanced pancreatic cancer.”
Hong explained what it’s like to witness the readout of these results.
“It’s gratifying to see results like this, since targeting mutant KRAS seemed virtually impossible just a few years ago,” he concluded. “Still, we must continue our research efforts to make progress against other common KRAS mutations found in pancreatic and other cancer types.”