Methods of Treating Cancer Using Anti-HER2 Antibody-Drug Conjugates and HER2 Kinase Inhibitors

A method for treating or preventing progression of cancer in an individual, comprising administering to the individual an effective amount of tucatinib and an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate that comprises an anti-HER2 antibody and a cytotoxic molecule;

• wherein the anti-HER2 antibody comprises a heavy chain comprising a heavy chain variable (VH) domain and a light chain comprising a light chain variable (VL) domain;
• wherein the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYIH (SEQ ID NO:1), a CDR-H2 comprising the amino acid sequence RVNPDHGDSYYNQKFKD (SEQ ID NO:2), and a CDR-H3 comprising the amino acid sequence ARNYLFDHW (SEQ ID NO:11);
• and wherein the VL domain comprises a CDR-L1 comprising the amino acid sequence KASQDVGTAVA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence WASIRHT (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence HQFATYT (SEQ ID NO:6).

The method of claim 2020 or claim 21, wherein the administration of tucatinib and the antibody-drug conjugate is a third-line or higher (3L+) treatment.

A kit comprising tucatinib and an anti-HER2 antibody-drug conjugate that comprises an anti-HER2 antibody and a cytotoxic molecule;

• wherein the anti-HER2 antibody comprises a heavy chain comprising a heavy chain variable (VH) domain and a light chain comprising a light chain variable (VL) domain;
• wherein the VH domain comprises a CDR-H1 comprising the amino acid sequence DYYIH (SEQ ID NO:1), a CDR-H2 comprising the amino acid sequence RVNPDHGDSYYNQKFKD (SEQ ID NO:2), and a CDR-H3 comprising the amino acid sequence NYLFDH (SEQ ID NO:3);
• wherein the VL domain comprises a CDR-L1 comprising the amino acid sequence KASQDVGTAVA (SEQ ID NO:4), a CDR-L2 comprising the amino acid sequence WASIRHT (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence HQFATYT (SEQ ID NO:6).