Dr Pietrantonio on the CodeBreak 300 Trial in KRAS G12C-mutated mCRC

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Filippo Pietrantonio, MD, discusses the influence of primary results from the phase 3 CodeBreak 300 trial of sotorasib plus panitumumab on KRAS G12C-mutated metastatic colorectal cancer.

Filippo Pietrantonio, MD, medical oncologist, Fondazione IRCCS Istituto Nazionale dei Tumori, discusses the primary results from the phase 3 CodeBreak 300 trial (NCT05198934) of sotorasib (Lumkras) plus panitumumab (Vectibix) in KRAS G12C–mutated metastatic colorectal cancer (mCRC).

This study compared sotorasib, a KRAS G12C-inhibitor, in combination with panitumumab, an anti-EGFR antibody, vs the standard of care (SOC) in patients with chemorefractory KRAS G12C–mutated mCRC who had progressed on 1 to 3 prior lines of therapy.

Pietrantonio explains that patients were randomly assigned to 1 of 3 dosing regimens: sotorasib at 960 mg daily plus intravenous (IV) panitumumab at 6 mg/kg, 240 mg of sotorasib daily plus IV panitumumab 6 mg/kg, or investigator's choice of regorafenib (Stivarga) or trifluridine/tipiracil (TAS-102; Lonsurf).

The study successfully met its primary end point, with both combination arms showing significantly improved progression-free survival (PFS) compared with SOC, Pietrantonio reports. The 960 mg dosing regimen demonstrated a clinically meaningful benefit in PFS, overall response rate, disease control rate, and duration of response, followed by the 240 mg dose, and the SOC. Overall survival (OS) data were not mature at the time of data cutoff. Regarding safety, the combination's toxicity profile was deemed manageable and consistent with that of the individual components, Pietrantonio states.

Overall, this study represents the first phase 3 trial evaluating a KRAS G12C inhibitor with an anti-EGFR antibody in chemorefractory mCRC, Pietrantonio says. The results indicate that sotorasib and panitumumab combinations elicit superior PFS and other efficacy outcomes, with manageable safety profiles compared to standard of care, he concludes.

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