David Sanghyun Hong (The University of Texas MD Anderson Cancer Center) | 한빛사논문 > 한빛사

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The University of Texas MD Anderson Cancer Center

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Nat. Med., Jan 04 2024, | https://doi.org/10.1038/s41591-023-02717-6 Sotorasib with panitumumab in chemotherapy-refractory KRASG12C-mutated colorectal cancer: a phase 1b trial

Yasutoshi Kuboki^1,14, Marwan Fakih^2,14, John Strickler^3,14, Rona Yaeger^4,14, Toshiki Masuishi⁵, Edward J. Kim⁶, Christine M. Bestvina⁷, Scott Kopetz⁸, Gerald S. Falchook⁹, Corey Langer¹⁰, John Krauss¹¹, Sonam Puri¹², Panli Cardona¹³, Emily Chan¹³, Tracy Varrieur¹³, Lata Mukundan¹³, Abraham Anderson¹³, Qui Tran¹³ & David S. Hong⁸

¹National Cancer Center Hospital East, Kashiwa, Japan.

²City of Hope Comprehensive Cancer Center, Duarte, CA, USA.

³Duke University Medical Center, Durham, NC, USA.

⁴Memorial Sloan Kettering Cancer Center, New York, NY, USA.

⁵Aichi Cancer Center Hospital, Nagoya, Japan.

⁶UC Davis Comprehensive Cancer Center, Sacramento, CA, USA.

⁷University of Chicago, Chicago, IL, USA.

⁸The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

⁹Sarah Cannon Research Institute, Nashville, TN, USA.

¹⁰University of Pennsylvania, Philadelphia, PA, USA.

¹¹University of Michigan, Ann Arbor, MI, USA. 12Huntsman Cancer Institute, Salt Lake City, UT, USA.

¹³Amgen Inc., Thousand Oaks, CA, USA.

¹⁴These authors contributed equally: Yasutoshi Kuboki, Marwan Fakih, John Strickler, Rona Yaeger.

Corresponding author : Correspondence to David S. Hong.

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 KRAS ^G12C-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 KRAS ^G12C-mutated metastatic colorectal cancer. ClinicalTrials.gov identifier: NCT04185883 .

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형식Research article
게재일2024년 01월 (BRIC 등록일 2024-01-23)
연구진국외 연구진
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