Sotorasibu plus panitumumab 960 mg appears as SOC in KRAS G12C+mCRC

Based on publishedCodeBreaK 300 Analyzing results from a phase 3 trial (NCT05198934), the survival and response rates of the 960 mg dose of sotorasib (AMG510) plus panitumumab (Panitumumab) were not statistically significant, but combined with the safety profile, support the use of this dose as a treatment option for chemotherapy-refractory KRAS Standard treatment for patients with G12C-mutated metastatic colorectal cancer (CRC).

At the time of data cutoff, the median follow-up time was 13.6 months, with 24 deaths occurring in the 960 mg/panitumumab group, 28 deaths occurring in the 240 mg/panitumumab group, and 30 deaths occurring in the investigator-selected treatment group. At the investigator's option, sotoracib 960 Median overall survival (OS) was not reached with mg/panitumumab (95% confidence interval [CI], 8.61 - not estimable [NE]), 11.9 months (95% CI, 7.52 - NE) with sotoraxib 240 mg/panitumumab, and 10.3 months (95% CI, 7.0 - NE).

Favorable OS trends for sotoraxib 960 mg/panitumumab were also observed in prespecified key subgroups, although the study authors noted that the small sample size resulted in a wide CI. For OS, the estimated HR for sotoraxib with 960 mg/panitumumab was 0.70 (95% CI, 0.41-1.18; P=0.20) with 240 The HR for mg/panitumumab sotoracib was 0.83 (95% CI, 0.49-1.39; P=0.50).

An ad hoc sensitivity analysis that adjusted for the confounding effect of initiating subsequent treatment of interest showed a stratified HR of 0.65 (95% CI, 0.28-1.37) for sotoraxib 960 mg/panitumumab and a stratified HR of 0.84 (95% CI, 0.44-1.58) for sotoraxib 240 mg/panitumumab. The updated objective response rates (ORR) were 30.2% (95%CI, 18.3%-44.3%), 7.5% (95%CI, 2.1%-18.2%) and 1.9% (95%CI, 0.0%-9.9%); no formal review of the ORR for each blinded independent central review was performed because OS did not reach statistical significance. The median duration of response in the sotoraxib 960 mg/panitumumab arm was 10.1 months (95% CI, 3.9-NE).

Taking into account all reported improved outcomes, this study supportsthe sustained therapeutic benefit of 960 mg sotorasiib/panitumumab as a new standard of care for patients with KRAS G12C-mutated chemotherapy-refractory [metastatic] CRC.

CodeBreaK 300 was a randomized, open-label trial evaluating the efficacy and safety of sotoraxib in combination with panitumumab as an investigator's treatment option in patients with previously treated metastatic CRC harboring the KRAS G12C mutation. A total of 160 patients were randomly assigned in a 1:1:1 ratio to receive 960 mg of sotoracib plus panitumumab ( n = 53), 240 mg of sotoracib Galpanitumab (n=52) or investigator choice (n=54; Lonsurf, n=37; Regorafenib, n=14).

Eligible patients are18 years of age or older, with pathologically documented metastatic colorectal cancer, associated with KRAS G12C mutation, and have received at least 1 treatment for metastatic disease. 2 Additionally, patients have an ECOG performance status of 2 or less and a life expectancy of at least 3 months based on RECIST v1.1 measurable disease. Exclusion criteria included active brain metastases, history of hematologic malignancy, leptomeningeal disease, and prior KRAS G12C inhibitor therapy. Key secondary endpoints are OS and ORR; other secondary endpoints are time to response, duration of response, disease control and safety.

Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 45.3% of patients in the 960 mg/panitumumab group, 34.0% in the 240 mg/panitumumab group, and 45.1% in the investigator-selected group; Grade 3 or higher treatment-related hepatotoxicity events occurred in 1.9%, 0%, and 2.0%, respectively. The most common adverse reactions with 960 mg/panitumumab were dermatitis acneiformis (17.0%), hypomagnesemia (7.5%), and rash (5.7%).

References:https://www.cancernetwork.com/view/sotorasib-at-960-mg-plus-panitumumab-emerges-as-soc-in-kras-g12c-mcrc