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 soluble hyaluronidase comprising a sequence of amino acids that has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% 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 an effective dose of an antibody-drug conjugate;
• or
• (ii) 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%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% 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
• subcutaneously administering to the patient in need thereof a second composition comprising an effective dose of an antibody-drug conjugate;
• wherein:
• the subcutaneous administration of the combination dosing regimen is administered in an amount that yields an area under the curve (AUC) that is substantially equivalent to the AUC of an intravenous administration of a dosing regimen comprising an effective dose of the antibody-drug conjugate without hyaluronidase, and/or
• the subcutaneous administration of the combination dosing regimen is administered in an amount that yields a maximum concentration (Cmax) that is lower than the Cmax of an intravenous administration of a dosing regimen comprising an effective dose of the antibody-drug conjugate without hyaluronidase.

A method of reducing at least one injection site side effect associated with subcutaneously administering an antibody-drug conjugate, the method comprising:

• (i) subcutaneously administering to a patient in need thereof a composition comprising a soluble hyaluronidase comprising a sequence of amino acids that has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% 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 an antibody-drug conjugate;
• or
• (ii) 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%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% 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
• subcutaneously administering to the patient in need thereof a second composition comprising an antibody-drug conjugate;
• wherein the at least one injection site side effect selected from swelling (bleb) volume, swelling (bleb) height, swelling (bleb) area, induration, back leakage, focal keratosis, and/or immune cell infiltrates is reduced in comparison to administration of the antibody-drug conjugate without hyaluronidase.