Sotorasib demonstrated “modest” antitumor activity in a phase 1/2 trial of previously treated patients with KRASG12C-mutant colorectal cancer (CRC), according to researchers.1

The study’s primary endpoint, objective response, did not reach the prespecified benchmark. However, researchers said the progression-free survival (PFS) and overall survival (OS) results were “notable” for this patient population.

These results, from the CodeBreaK100 trial, were published in The Lancet Oncology.

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The trial ( Identifier: NCT03600883) was designed to test sotorasib in patients with solid tumors. In a prior analysis, sotorasib produced an objective response rate (ORR) of 7.1%, a disease control rate (DCR) of 74%, and a median PFS of 4.0 months in patients with KRASG12C-mutant solid tumors.2

The current analysis included a subset of 62 patients with advanced KRASG12C-mutant CRC who had progressed after receiving fluoropyrimidine, oxaliplatin, and irinotecan.

Patients were treated with oral sotorasib (960 mg once per day) until disease progression, unacceptable toxicity, withdrawal, or death. The primary endpoint was ORR by blinded independent central review.

The patients’ median age was 56.0 years (interquartile range [IQR], 49.0-61.0), and 55% were women. Patients had received a median of 3 prior lines of therapy (IQR, 2-4).

At the data cutoff (March 1, 2021), the median duration of treatment was 18 weeks. The trial is ongoing, and 5 CRC patients were still receiving sotorasib at the cutoff.

The ORR was 9.7% (n=6), and all responses were partial responses. The DCR was 82.3% (n=51), and tumor shrinkage occurred in 66% of patients (n=41). Among all responders, the median percentage of best tumor shrinkage was 46.3%. Progressive disease was seen in 18% of patients (n=11).

At a median follow-up of 11.0 months, the median PFS was 4.0 months. The estimated PFS was 21.9% at 6 months and 11.7% at 12 months.

At a median follow-up of 11.4 months, the median OS was 10.6 months. The estimated 12-month OS rate was 42.5%. Death due to any cause was reported in 53% of patients (n=33).

Grade 3 treatment-related adverse events (TRAEs) occurred in 6 patients, the most common being diarrhea (n=2). There was 1 grade 4 TRAE (increased blood creatine phosphokinase). Serious TRAEs were reported in 2 patients (back pain and acute kidney injury), and there were no fatal events. 

“Although the 9.7% overall response rate did not reach the benchmark, oral administration of sotorasib once per day showed modest antitumor activity and manageable safety in these heavily pretreated, chemo-refractory patients,” the researchers wrote. “Sotorasib is under evaluation in combination with other therapeutics to increase potential activity and overcome potential resistance mechanisms.”

Disclosures: This research was supported by Amgen. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


1. Fakih MG, Kopetz S, Kuboki Y, et al. Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): A prespecified analysis of a single-arm, phase 2 trial. Lancet Oncol. Published Online December 14, 2021. doi:10.1016/S1470-2045(21)00605-7

2. Hong DS, Fakih MG, Strickler JH, et al. KRAS(G12C) inhibition with sotorasib in advanced solid tumors. N Engl J Med. 2020;383:1207-17. doi:10.1056/NEJMoa1917239