Amgen today announced the presentation of efficacy and safety data from the CodeBreaK 100 Phase 1/2 trial in patients with KRAS G12C-mutated advanced pancreatic cancer who received LUMAKRAS® (sotorasib). The data will be presented at the monthly American Society of Clinical Oncology (ASCO) Plenary Series on Feb. 15, 2022. Data show encouraging and clinically meaningful anticancer activity and a positive benefit:risk profile.
“Based on these exciting data, we are expanding CodeBreaK 100 to enroll more patients with pancreatic and other tumor types to better understand the efficacy and safety of LUMAKRAS in tumors outside of non-small cell lung and colorectal cancers,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “CodeBreaK is the largest and broadest global clinical trial program to date with one of the most robust, centrally reviewed datasets. As we learn more from the extensive data that we collect, we’ll continue to invest in the program by expanding cohorts and exploring new combinations so that we can help as many patients as possible.”
LUMAKRAS demonstrated a centrally confirmed objective response rate (ORR) of 21% and disease control rate (DCR) of 84% across 38 heavily pre-treated advanced pancreatic cancer patients. Nearly 80% of patients received LUMAKRAS as a third-line or later therapy. Eight of the 38 patients achieved a confirmed partial response (PR) performed by a blinded independent central review (BICR). Two of the eight patients with PR have ongoing responses. Median duration of response was 5.7 months with a median follow-up of 16.8 months as of the data cutoff date of Nov. 1, 2021. The results also show a median progression free survival (PFS) of 4 months and a median overall survival (OS) of almost 7 months. No new safety signals were identified with this study of patients with advanced pancreatic cancers. Treatment-related adverse events (TRAEs) of any grade occurred in 16 (42%) patients with diarrhea (5%) and fatigue (5%) as the most common grade 3 TRAEs. No TRAEs were fatal or resulted in treatment discontinuation.
“After decades of research, current treatments for patients with pancreatic cancer provide limited survival benefit, illustrating the critical need for novel, safe and effective treatment options,” said John Strickler, M.D. associate professor of medicine, Duke University School of Medicine and gastrointestinal oncologist. “In the largest dataset evaluating the efficacy and safety of a KRASG12C inhibitor in heavily pretreated advanced pancreatic cancer, sotorasib achieved a centrally confirmed response rate of 21% and a disease control rate of 84%. This is clinically meaningful for patients because there is not an established standard therapy for these patients once they get to a third-line of treatment.”
Cancer of the pancreas is a highly lethal malignancy. It is the fourth leading cause of cancer-related deaths in both men and women in the U.S. with a 5-year survival rate of approximately 10%. There is a high unmet need for patients with advanced pancreatic cancer that has progressed after first-line treatment, where FDA-approved second-line therapy has provided survival of about six months and a response rate of 16%. After progression on first- and second-line chemotherapy, there are no therapies with a demonstrated survival benefit. Despite advances in treatment, few improvements have been made to improve diagnosis and treatment of pancreatic cancer.
It is estimated that approximately 90% of patients with pancreatic cancer harbor a KRAS mutation with KRAS G12C accounting for approximately 1-2% of these mutations.
