In the phase I/II CodeBreaK 100 trial reported in The New England Journal of Medicine, John H. Strickler, MD, and colleagues found that the KRAS G12C inhibitor sotorasib showed activity in previously treated patients with advanced pancreatic cancer and a KRAS G12C mutation.

John H. Strickler, MD

Study Details

In the trial, 38 patients were enrolled from sites in seven countries between July 2019 and January 2021, including 12 in phase I of the study and 26 in phase II. All 38 patients received oral sotorasib at 960 mg daily until disease progression or unacceptable toxicity and were included in analysis of outcomes. Patients had received a median of two lines (range = 1–8 lines) of prior therapy.

Responses

Objective responses (all partial) on blinded independent central review were observed in 8 (21%, 95% confidence interval [CI] = 10%–37%) of 38 patients. Median time to response was 1.5 months (range = 1.3–5.6 months) and median duration of response was 5.7 months (95% CI = 1.6 months to not evaluable). An additional 24 patients (63%) had stable disease, yielding a disease control rate of 84%. Tumor shrinkage of target lesions of any magnitude was observed in 30 patients (79%).

Median progression-free survival was 4.0 months (95% CI = 2.8-5.6 months); rates at 6 and 9 months were 31.6% and 9.9%. A total of 10 patients received subsequent anticancer therapy, primarily chemotherapy. At a median follow-up of 16.8 months (95% CI = 9.5 months to not evaluable), median overall survival was 6.9 months (95% CI = 5.0–9.1 months), with a 12-month rate of 19.6%.

Adverse Events

Treatment-related adverse events of any grade occurred in 42% of patients and were grade 3 in six patients (16%), most commonly diarrhea and fatigue in two patients (5%) each. No treatment-related grade 4 or 5 adverse events were reported. Treatment-related serious adverse events occurred in three patients (8%). Treatment-related adverse events led to dose reduction or interruption of treatment in five patients (13%); no treatment-related adverse events led to discontinuation of treatment.

The investigators concluded, “Sotorasib showed anticancer activity and had an acceptable safety profile in patients with KRAS G12C–mutated advanced pancreatic cancer who had received previous treatment.”

David S. Hong, MD, of the Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, is the corresponding author for The New England Journal of Medicine article.

Disclosure: The study was funded by Amgen, grants from the National Cancer Institute, and others. For full disclosures of the study authors, visit nejm.org.