Background: Pmab is a fully human monoclonal antibody against the epidermal growth factor receptor (EGFR). Significant improvement in progression-free survival (PFS) was demonstrated in pts with wild-type (WT) KRAS mCRC treated with pmab+FOLFOX4 (1^st-line; study 20050203), pmab+FOLFIRI (2^nd-line; study 20050181), and pmab monotherapy (study 20020408). In mCRC, mutations in KRAS codons 12 and 13 are established biomarkers for lack of clinical benefit to anti-EGFR therapies. We retrospectively examined individual MT KRAS codon 12 and 13 alleles as prognostic and predictive biomarkers of response in three phase 3 studies. Methods: Pts were randomized to receive FOLFOX4, FOLFIRI, or best supportive care +/- pmab 6.0 mg/kg Q2W in studies 20050203, 20050181, and 20020408, respectively. The MT KRAS codon 12 and 13 alleles (G12A, G12C, G12D, G12R, G12S, G12V, G13D) were detected using the Therascreen K-RAS Mutation Kit (Qiagen). Results: MT KRAS codon 12 and 13 alleles were detected in 40% (440/1096), 45% (486/1083), and 43% (184/427) of pts in studies 20050203, 20050181, and 20020408, respectively. MT KRAS allele distribution was conserved across studies and balanced between treatment arms. Baseline demographic and clinical features were comparable between all MT KRAS allele subgroups. Across all studies, no single MT KRAS allele was consistently prognostic for PFS or overall survival (OS) in the control arm-treated pts. Similarly, no single MT KRAS allele was a consistent positive or negative predictive factor for PFS or OS in pmab-treated pts. Only in the pmab+FOLFOX4 arm of study 20050203 were G13D (unfavorably) and G12V (favorably) significantly associated with OS. Response rates were similar between MT KRAS allele groups in the 1^st- and 2^nd-line mCRC treatment setting. Finally, in analyses of pts pooled from all 3 trials, only the G12A KRAS allele emerged as a significant negative predictive factor for OS. Conclusions: The lack of consistent results across three lines of therapy indicates pts with MT KRAS codon 12 or 13 alleles are unlikely to respond to pmab therapy. Currently, only pts with WT KRAS mCRC should be treated with pmab.