Compositions and methods for predicting response to NaPi2b-targeted therapy

A method of treating a cancer in a subject with a NaPi2b-targeted antibody drug conjugate comprising:

• a. measuring the expression level of NaPi2b in a tumor sample obtained from the subject by contacting the tumor sample with a chimeric anti-NaPi2b antibody, wherein the chimeric anti-NaPi2b antibody comprises a human variable region and a rabbit constant region,
• wherein the human variable region comprises:
• a variable heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence GYTFTGYNIH (SEQ ID NO:
• 3), a variable heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence AIYPGNGDTSYKQKFRG (SEQ ID NO:
• 4), a variable heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence GETARATFAY (SEQ ID NO:
• 5), a variable light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence SASQDIGNFLN (SEQ ID NO:
• 6), a variable light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence YTSSLYS (SEQ ID NO:
• 7), a variable light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence QQYSKLPLT (SEQ ID NO:
• 8), and
• the rabbit constant region comprises a heavy chain constant region comprising the amino acid sequence of SEQ ID NO:
• 11 and a light chain constant region comprising the amino acid sequence of SEQ ID NO:12;
• b. predicting that the subject will be responsive to treatment when the expression level of NaPi2b in the tumor sample is higher than a predetermined quantitative or semi quantitative cut-off score;
• and
• c. administering the NaPi2b-targeted antibody drug conjugate to a subject predicted to be responsive;
• wherein the NaPi2b-targeted antibody conjugate comprises the NaPi2b-targeted antibody, XMT-1535 comprising a variable heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence GYTFTGYNIH (SEQ ID NO:
• 3), a variable heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence AIYPGNGDTSYKQKFRG (SEQ ID NO:
• 4), a variable heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence GETARATFAY (SEQ ID NO:
• 5), a variable light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence SASQDIGNFLN (SEQ ID NO:
• 6), a variable light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence YTSSLYS (SEQ ID NO:
• 7), a variable light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence QQYSKLPLT (SEQ ID NO:
• 8).