The present invention relates to methods of cancer therapy using subcutaneous administration of antibody-drug conjugates (ADCs). Preferably, the ADC comprises an antibody that binds to Trop-2, CEACAM5, CEACAM6, CD20, CD22, CD30, CD46, CD74, Her-2, folate receptor, or HLA-DR. More preferably, the drug is SN-38. Subcutaneous administration is at least as effective as intravenous administration of the same ADC. Surprisingly, subcutaneous administration can be used without inducing unmanageable adverse local toxicity at the injection site. Subcutaneous administration is advantageous in requiring less frequent administration, substantially reducing the amount of time required for intravenous administration, and reducing the levels of systemic toxicities observed with intravenous administration. When administered at specified dosages and schedules, the ADCs can reduce solid tumors in size, reduce or eliminate metastases and are effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.
