Prediction of effect of a c-Met inhibitor using mutation of KRAS or BRAF

A method for predicting efficacy of a c-Met inhibitor in a subject or selecting a subject suitable for the application of a c-Met inhibitor, the method comprising:

• testing for a mutation of KRAS protein in an amino acid position corresponding to one or more of positions 12, 13, 23, 24, 59, 61, or 146 of SEQ ID NO:
• 109, or a corresponding mutation in a nucleic acid encoding KRAS protein, in a biological sample from a subject;
• and
• determining that a c-Met inhibitor would have efficacy in the subject or selecting the subject from which the biological sample is obtained for the application of the c-Met inhibitor, when
• a mutation of KRAS protein or nucleic acid encoding KRAS is not detected in the biological sample,
• further comprising a step of administering the c-Met inhibitor to the subject for whom it is determined that a c-Met inhibitor would have efficacy in the subject or who is selected for the application of the c-Met inhibitor, wherein the c-Met inhibitor comprises an anti-c-Met antibody or an antigen-binding fragment thereof that comprises:
• a CDR-H1 comprising SEQ ID NO:
• 4;
• a CDR-H2 comprising SEQ ID NO:
• 5, SEQ ID NO:
• 2, or an amino acid sequence comprising 8-19 consecutive amino acids within SEQ ID NO:
• 2 including the 3rd to 10th positions of SEQ ID NO:
• 2;
• and a CDR-H3 comprising SEQ ID NO:
• 6, SEQ ID NO:
• 85, or an amino acid sequence comprising 6-13 consecutive amino acids within SEQ ID NO:
• 85 including the 1st to 6th positions of the amino acid sequence of SEQ ID NO:
• 85;
• and
• a CDR-L1 comprising SEQ ID NO:
• 7, a CDR-L2 comprising SEQ ID NO:
• 8, and a CDR-L3 comprising SEQ ID NO:
• 15.

A method for predicting efficacy of a c-Met inhibitor in a subject or selecting a subject suitable for the application of a c-Met inhibitor, the method comprising:

• testing a biological sample from a subject for
• (a) at least one amino acid mutation of KRAS selected from the group consisting of G12A, G12D, G12R, G12C, G12S, G12V, A146T, A59T, L23R, G13N, G13D, I24F, Q61L, Q61H, G13C, and Q61K, based on the amino acid sequence of SEQ ID NO:
• 109;
• or a mutation in a nucleic acid encoding a KRAS protein causing the at least one amino acid mutation;
• and (b) at least one amino acid mutation of BRAF protein selected from the group consisting of G596R, V600E, V600K, V600R, K601E, D594A, K601E, G469A, V600M, G469A, V600L, G466V, V600D, G469V, D594G, D594N, N581S, L597V, L597S, L597Q, K601N, G466V, G466E, G464V, and G469E, based on the amino acid sequence of SEQ ID NO:
• 110;
• or a mutation in a nucleic acid encoding a BRAF protein causing the at least one amino acid mutation;
• determining that a c-Met inhibitor would have efficacy in the subject or selecting the subject from which the biological sample is obtained for the application of the c-Met inhibitor, when the at least one mutation of KRAS protein is not detected and the at least one mutation of BRAF protein is not detected;
• and administering the c-Met inhibitor to the subject for whom it is determined that a c-Met inhibitor would have efficacy in the subject or who is selected for the application of the c-Met inhibitor.