Combination therapy with antibody-drug conjugates and hyaluronidases

A method of reducing at least one injection site side effect associated with subcutaneously administering an antibody-drug conjugate (ADC), the method 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%, 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 (b) a therapeutically effective dose of the 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%, 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 (b) subcutaneously administering to the patient in need thereof a second composition comprising a therapeutically effective dose of the ADC;
• wherein the at least one injection site side effect is at least one of swelling (bleb) volume, swelling (bleb) height, swelling (bleb) area, induration, back leakage, focal keratosis, and immune cell infiltrates and wherein the at least one injection site side effect is reduced in comparison to an administration of the ADC without the soluble hyaluronidase.