1. Sotorasib with panitumumab in chemotherapy-refractory KRASG12C-mutated colorectal cancer: a phase 1b trial.
- Author
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Kuboki, Yasutoshi, Fakih, Marwan, Strickler, John, Yaeger, Rona, Masuishi, Toshiki, Kim, Edward, Bestvina, Christine, Kopetz, Scott, Falchook, Gerald, Langer, Corey, Krauss, John, Puri, Sonam, Cardona, Panli, Chan, Emily, Varrieur, Tracy, Mukundan, Lata, Anderson, Abraham, Tran, Qui, and Hong, David
- Subjects
Humans ,Panitumumab ,Proto-Oncogene Proteins p21(ras) ,Antibodies ,Monoclonal ,Colorectal Neoplasms ,ErbB Receptors ,Mutation ,Antineoplastic Combined Chemotherapy Protocols ,Piperazines ,Pyridines ,Pyrimidines - Abstract
The current third-line (and beyond) treatment options for RAS-mutant metastatic colorectal cancer have yielded limited efficacy. At the time of study start, the combination of sotorasib, a KRAS (Kirsten rat sarcoma viral oncogene homolog)-G12C inhibitor, and panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, was hypothesized to overcome treatment-induced resistance. This phase 1b substudy of the CodeBreaK 101 master protocol evaluated sotorasib plus panitumumab in patients with chemotherapy-refractory KRASG12C-mutated metastatic colorectal cancer. Here, we report the results in a dose-exploration cohort and a dose-expansion cohort. Patients received sotorasib (960 mg, once daily) plus panitumumab (6 mg kg-1, once every 2 weeks). The primary endpoints were safety and tolerability. Secondary endpoints included efficacy and pharmacokinetics. Exploratory biomarkers at baseline were assessed. Forty-eight patients (dose-exploration cohort, n = 8; dose-expansion cohort, n = 40) were treated. Treatment-related adverse events of any grade and grade ≥3 occurred in 45 (94%) and 13 (27%) patients, respectively. In the dose-expansion cohort, the confirmed objective response rate was 30.0% (95% confidence interval (CI) 16.6%, 46.5%). Median progression-free survival was 5.7 months (95% CI 4.2, 7.7 months). Median overall survival was 15.2 months (95% CI 12.5 months, not estimable). Prevalent genomic coalterations included APC (84%), TP53 (74%), SMAD4 (33%), PIK3CA (28%) and EGFR (26%). Sotorasib-panitumumab demonstrated acceptable safety with promising efficacy in chemotherapy-refractory KRASG12C-mutated metastatic colorectal cancer. ClinicalTrials.gov identifier: NCT04185883 .
- Published
- 2024