Methods of using bispecific antigen-binding constructs targeting her2

A method of treating a subject having a tumor comprising administering to the subject a pharmaceutical composition comprising an effective amount of an antigen binding construct and a pharmaceutically acceptable carrier, wherein the antigen binding construct comprises:

• a) a first antigen-binding polypeptide construct which monovalently and specifically binds a HER2 (human epidermal growth factor receptor 2) ECD2 (extracellular domain 2) region on a HER2-expressing cell and comprising:
• a first antigen-binding polypeptide construct which monovalently and specifically binds a HER2 (human epidermal growth factor receptor 2) ECD2 extracellular domain 2) region on a HER2-expressing cell and comprises a first heavy chain variable domain and a first light chain variable domain,
• wherein the first heavy chain variable domain comprises three first heavy chain CDR sequences comprising CDR-H1 comprising SEQ ID NO:
• 101, CDR-H2 comprising SEQ ID NO:
• 105, and CDR-H3 comprising SEQ ID NO:
• 103 and
• wherein the first light chain variable domain comprises three first light chain CDR sequences comprising CDR-L1 comprising SEQ ID NO:
• 73, CDR-L2 comprising SEQ ID NO:
• 77, and CDR-L3 comprising SEQ ID NO:
• 75;
• and
• b) a second antigen-binding polypeptide construct which monovalently and specifically binds HER2 ECD4 (extracellular domain 4) region on a HER2-expressing cell and comprising a second heavy chain variable domain and a second light chain variable domain,
• wherein the second heavy chain variable domain comprises three second heavy chain CDR sequences comprising CDR-H1 comprising SEQ ID NO:
• 307, CDR-H2 comprising SEQ ID NO:
• 311, and CDR-H3 comprising SEQ ID NO:
• 309, and
• wherein the second light chain variable domain comprises three second light chain CDR sequences comprising CDR-L1 comprising SEQ ID NO:
• 299, CDR-L2 comprising SEQ ID NO:
• 303, and CDR-L3 comprising SEQ ID NO:
• 301;
• c) first and second linker polypeptides, wherein the first polypeptide is operably linked to the first antigen-binding polypeptide construct;
• wherein first antigen binding polypeptide is a Fab and the second antigen polypeptide construct is an scFv, and
• wherein the antigen binding construct is administered to the subject once every 14 days at a dose of at least 10 mg of antigen binding construct per kg of body weight or once every 14 days at a dose of at least 15 mg of antigen binding construct per kg of body weight or once every 14 days at a dose of at least 20 mg of antigen binding construct per kg of body weight or once every 21 days at a dose of at least 15 mg of antigen binding construct per kg of body weight or once every 21 days at a dose of at least 20 mg of antigen binding construct per kg of body weight,
• thereby treating the subject having the tumor.