Combination therapy with antibody-drug conjugates and hyaluronidases

A combination dosing regimen, comprising:

• (i) subcutaneously administering to a patient in need thereof a composition comprising (a) a soluble hyaluronidase comprising a sequence of amino acids that has at least 85% sequence identity to a sequence of amino acids that contains at least amino acids 36-464 of SEQ ID NO:
• 1 and retains hyaluronidase activity, and (b) an effective dose of an antibody-drug conjugate (ADC);
• or
• (ii) (a) subcutaneously administering to a patient in need thereof a first composition comprising a soluble hyaluronidase comprising a sequence of amino acids that has at least 85% sequence identity to a sequence of amino acids that contains at least amino acids 36-464 of SEQ ID NO:
• 1 and retains hyaluronidase activity, and (b) subcutaneously administering to the patient in need thereof a second composition comprising the effective dose of the ADC,
• wherein:
• the subcutaneous administration of the combination dosing regimen is administered in an amount that yields an area under the curve (AUC) of the ADC that is equal or greater than an AUC of an intravenous administration of a dosing regimen comprising the effective dose of the ADC without the soluble hyaluronidase, and
• the subcutaneous administration of the combination dosing regimen yields a maximum concentration (Cmax) of the ADC that is lower than the Cmax of the ADC obtained from the intravenous administration of the dosing regimen without the soluble hyaluronidase.