Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2024 Jan;30(1):265-270.
doi: 10.1038/s41591-023-02717-6. Epub 2024 Jan 4.

Sotorasib with panitumumab in chemotherapy-refractory KRASG12C-mutated colorectal cancer: a phase 1b trial

Yasutoshi Kuboki #  1 , Marwan Fakih #  2 , John Strickler #  3 , Rona Yaeger #  4 , Toshiki Masuishi  5 , Edward J Kim  6 , Christine M Bestvina  7 , Scott Kopetz  8 , Gerald S Falchook  9 , Corey Langer  10 , John Krauss  11 , Sonam Puri  12 , Panli Cardona  13 , Emily Chan  13 , Tracy Varrieur  13 , Lata Mukundan  13 , Abraham Anderson  13 , Qui Tran  13 , David S Hong  14
Affiliations
Clinical Trial

Sotorasib with panitumumab in chemotherapy-refractory KRASG12C-mutated colorectal cancer: a phase 1b trial

Yasutoshi Kuboki et al. Nat Med. 2024 Jan.

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 .

PubMed Disclaimer

Figures

Figure 1.
Figure 1.. Study schema
Additional cohorts that are not the subject of this manuscript are not shown. * If dose level 1 was deemed not tolerable from toxicity primarily from panitumumab, a dose level using panitumumab at 3 mg/kg Q2W could be explored with or without dose reduction of sotorasib. CRC, colorectal cancer; RP2D, recommended phase 2 dose; Q2W, once every 2 weeks.
Figure 2.
Figure 2.. Patient disposition
N, number of patients in the analysis set; n, number of patients with observed data.
Figure 3.
Figure 3.. Activity of sotorasib therapy in the dose-expansion cohort
(A) Swimmer plot of duration of treatment and response as of data cutoff. (B) Best percentage change from baseline in sum of diameters (C) Kaplan-Meier curve of progression-free survival; Vertical lines indicate censoring. (D) Kaplan-Meier curve of overall survival; Vertical lines indicate censoring. Part 1A denotes the dose-exploration cohort and Part 2A denotes the dose-expansion cohort. BOR, best objective response; CRC, colorectal cancer; PD, progressive disease; PR, partial response; SD, stable disease.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71, 209–249 (2021). - PubMed
    1. Siegel RL, Miller KD, Wagle NS & Jemal A Cancer statistics, 2023. 73, 17–48 (2023). - PubMed
    1. Benson AB, et al. Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 19, 329–359 (2021). - PubMed
    1. Grothey A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381, 303–312 (2013). - PubMed
    1. Mayer RJ, et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med 372, 1909–1919 (2015). - PubMed

Publication types

MeSH terms

Associated data