As reported in the Journal of Clinical Oncology by Tanios S. Bekaii-Saab, MD, and colleagues, findings in the phase II cohort of the KRYSTAL-1 trial showed activity of adagrasib in patients with KRAS G12C–mutated advanced solid tumors. As noted by the investigators, the KRAS G12C inhibitor adagrasib has shown activity in patients with KRAS G12C–mutant non–small cell lung cancer (NSCLC) and colorectal cancer; these mutations occur infrequently in other solid tumor types.
Tanios S. Bekaii-Saab, MD
Study Details
In the U.S. multicenter study, 64 patients with KRAS G12C–mutated advanced solid tumors, excluding NSCLC and colorectal cancer, were enrolled between March 2020 to September 2022. A total of 63 patients were treated with adagrasib at 600 mg twice daily; treatment continued until disease progression or unacceptable toxicity. Patients had received a median of two lines (range = 0–7) of prior systemic therapy. The most common tumors were pancreatic (n = 21) and biliary tract (n = 12). The primary endpoint was objective response rate.
Key Results
Among 57 patients with measurable disease at baseline, objective responses (all partial) on blinded independent central review were observed in 20 patients (35.1%, 95% confidence interval [CI] = 22.9%–48.9%). The median duration of response was 5.3 months (95% CI = 2.8–7.3 months). Responses were observed in 7 of 21 patients (33.3%) with pancreatic cancer and 5 of 12 patients (41.7%) with biliary tract cancer. An additional 29 patients (50.9%) had stable disease.
Median follow-up was 16.8 months. Median progression-free survival among 57 patients with measurable disease at baseline was 7.4 months (95% CI = 5.3–8.6 months). Median overall survival among all 64 enrolled patients was 14.0 months (95% CI = 8.5–18.6 months).
Adverse Events
Among 63 patients in the safety population, the most common treatment-related adverse events of any grade reported were nausea (49.2%), diarrhea (47.6%), fatigue (41.3%), and vomiting (39.7%). Grade 3 or 4 treatment-related adverse events (one grade 4 event was reported) occurred in 27.0% of patients, most commonly fatigue (6.3%) and QT prolongation (6.3%). No patients discontinued adagrasib because of treatment-related adverse events. No treatment-related deaths were reported.
The investigators concluded: “Adagrasib demonstrates encouraging clinical activity and is well tolerated in this rare cohort of pretreated patients with KRAS G12C–mutated solid tumors.”
Dr. Bekaii-Saab, of the Department of Medical Oncology and Hematology, Mayo Clinic, Scottsdale, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by a National Cancer Institute grant and by Mirati Therapeutics, Inc. For full disclosures of the study authors, visit ascopubs.org.
