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CodeBreaK 300

Needs review

A Phase 3 Multicenter, Randomized, Open-label, Active-controlled Study of Sotorasib and Panitumumab Versus Investigator's Choice (Trifluridine and Tipiracil, or Regorafenib) for the Treatment of Previously Treated Metastatic Colorectal Cancer Subjects With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation

Phase 3N = 160NCT05198934

Population
Chemorefractory metastatic colorectal cancer with mutated KRAS G12C and no previous KRAS G12C inhibitor
Design
Open-label, randomised phase 3 trial, 1:1:1 allocation to sotorasib 960 mg plus panitumumab, sotorasib 240 mg plus panitumumab, or investigator's choice of trifluridine-tipiracil or regorafenib. The primary endpoint was progression-free survival by blinded independent central review (RECIST 1.1); overall survival and objective response were key secondary endpoints. Crossover was permitted after the primary analysis.
Primary endpoint
PFS
Arms
  • Investigator's choice (control, n = 54): Trifluridine-tipiracil or regorafenib
  • Sotorasib 240 mg + panitumumab (experimental, n = 53): Sotorasib 240 mg once daily plus panitumumab
  • Sotorasib 960 mg + panitumumab (experimental, n = 53): Sotorasib 960 mg once daily plus panitumumab
People
Fakih MG
PFSHR 0.49 (95% CI 0.3–0.8)Δ median PFS+3.4 monthsPFSHR 0.58 (95% CI 0.36–0.93)Δ median PFS+1.7 monthsΔ ORR+26.4 pointsOSHR 0.70 (95% CI 0.41–1.18)
Show the numbers
Results reported for CodeBreaK 300
EndpointAnalysisSotorasib 240 mg + panitumumab / Sotorasib 960 mg + panitumumabInvestigator's choiceEffect
PFSAll randomised patients (analysis population not stated in the abstract)Progression-free survival by blinded independent central review, sotorasib 960 mg + panitumumab versus investigator's choice (primary endpoint)primarymedian follow-up 7.8 monthsFakih 2023median 5.6 months (4.2–6.3)median 2.2 months (1.9–3.9)HR 0.49 (95% CI 0.3–0.8)P=0.006The published NEJM paper has a separate erratum (PMID 39938112) whose content could not be accessed; values are as in the original abstract.
PFSAll randomised patients (analysis population not stated in the abstract)Progression-free survival by blinded independent central review, sotorasib 240 mg + panitumumab versus investigator's choice (primary endpoint)primarymedian follow-up 7.8 monthsFakih 2023median 3.9 months (3.7–5.8)median 2.2 months (1.9–3.9)HR 0.58 (95% CI 0.36–0.93)P=0.03
ORRAll randomised patients (analysis population not stated in the abstract)Objective response (key secondary endpoint)primarymedian follow-up 7.8 monthsFakih 202326.4% (15.3–40.3%)0% (0.0–6.6%)—
OSAll randomised patients (analysis population not stated in the abstract)Overall survival, sotorasib 960 mg + panitumumab versus investigator's choice (key secondary endpoint)long term-updatemedian follow-up 13.6 monthsPietrantonio 2025——HR 0.70 (95% CI 0.41–1.18)P=0.20Prespecified at 50% maturity (about 80 deaths); the authors state the analysis was not adequately powered. Deaths: 24 (sotorasib 960 mg), 28 (sotorasib 240 mg) and 30 (investigator's choice). Crossover from investigator's choice was permitted after the primary analysis. Two-sided P value.
OSAll randomised patients (analysis population not stated in the abstract)Overall survival, sotorasib 240 mg + panitumumab versus investigator's choice (key secondary endpoint)long term-updatemedian follow-up 13.6 monthsPietrantonio 2025——HR 0.83 (95% CI 0.49–1.39)P=0.50Same analysis as the sotorasib 960 mg comparison; two-sided P value.
ORRAll randomised patients (analysis population not stated in the abstract)Updated objective response ratelong term-updatemedian follow-up 13.6 monthsPietrantonio 202530.2% (18.3–44.3%)1.9% (0.0–9.9%)—
Results reported for CodeBreaK 300
EndpointAnalysisSotorasib 240 mg + panitumumab / Sotorasib 960 mg + panitumumabInvestigator's choiceEffect
PFSAll randomised patients (analysis population not stated in the abstract)Progression-free survival by blinded independent central review, sotorasib 960 mg + panitumumab versus investigator's choice (primary endpoint)primarymedian follow-up 7.8 monthsFakih 2023median 5.6 months (4.2–6.3)median 2.2 months (1.9–3.9)HR 0.49 (95% CI 0.3–0.8)P=0.006The published NEJM paper has a separate erratum (PMID 39938112) whose content could not be accessed; values are as in the original abstract.
PFSAll randomised patients (analysis population not stated in the abstract)Progression-free survival by blinded independent central review, sotorasib 240 mg + panitumumab versus investigator's choice (primary endpoint)primarymedian follow-up 7.8 monthsFakih 2023median 3.9 months (3.7–5.8)median 2.2 months (1.9–3.9)HR 0.58 (95% CI 0.36–0.93)P=0.03
ORRAll randomised patients (analysis population not stated in the abstract)Objective response (key secondary endpoint)primarymedian follow-up 7.8 monthsFakih 202326.4% (15.3–40.3%)0% (0.0–6.6%)—
OSAll randomised patients (analysis population not stated in the abstract)Overall survival, sotorasib 960 mg + panitumumab versus investigator's choice (key secondary endpoint)long term-updatemedian follow-up 13.6 monthsPietrantonio 2025——HR 0.70 (95% CI 0.41–1.18)P=0.20Prespecified at 50% maturity (about 80 deaths); the authors state the analysis was not adequately powered. Deaths: 24 (sotorasib 960 mg), 28 (sotorasib 240 mg) and 30 (investigator's choice). Crossover from investigator's choice was permitted after the primary analysis. Two-sided P value.
OSAll randomised patients (analysis population not stated in the abstract)Overall survival, sotorasib 240 mg + panitumumab versus investigator's choice (key secondary endpoint)long term-updatemedian follow-up 13.6 monthsPietrantonio 2025——HR 0.83 (95% CI 0.49–1.39)P=0.50Same analysis as the sotorasib 960 mg comparison; two-sided P value.
ORRAll randomised patients (analysis population not stated in the abstract)Updated objective response ratelong term-updatemedian follow-up 13.6 monthsPietrantonio 202530.2% (18.3–44.3%)1.9% (0.0–9.9%)—
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSPFSOSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.490.3–0.8
PFS0.580.36–0.93
OS0.70.41–1.18
OS0.830.49–1.39
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%02468101214Months (modelled)
  • Sotorasib 960 mg + panitumumab (experimental)
  • Investigator's choice (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsSotorasib 960 mg + panitumumabInvestigator's choice
0100.0%100.0%
461.0%28.4%
742.0%11.0%
1125.6%3.1%
1417.7%1.2%
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%02468Months (modelled)
  • Sotorasib 240 mg + panitumumab (experimental)
  • Investigator's choice (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsSotorasib 240 mg + panitumumabInvestigator's choice
0100.0%100.0%
270.1%53.3%
541.1%20.7%
728.8%11.0%
1016.9%4.3%
Primary publication: Fakih MG, Salvatore L, Esaki T, Modest DP, Lopez-Bravo DP, Taieb J, et al. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023;389(23):2125-2139. PubMedDOI

Appears in

Sources

  1. Fakih MG, Salvatore L, Esaki T, Modest DP, Lopez-Bravo DP, Taieb J, et al. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023;389(23):2125-2139.

    PubMedDOI

  2. Pietrantonio F, Salvatore L, Esaki T, Modest DP, Lopez-Bravo DP, Taieb J, et al. Overall Survival Analysis of the Phase III CodeBreaK 300 Study of Sotorasib Plus Panitumumab Versus Investigator's Choice in Chemorefractory KRAS G12C Colorectal Cancer. J Clin Oncol. 2025;43(19):2147-2154.

    PubMedDOI