Abstract: The disclosure provides methods and compositions for treating tumors, particularly HER2-expressing tumors. The method comprises administering a therapeutically effective amount of a HER2/4-1BB bispecific fusion protein. The HER2/4-1BB bispecific fusion protein may be administered at a first dose and, subsequently, at a second dose, wherein the first dose exceeds the second dose.

Abstract: The disclosure provides methods for predicting a positive clinical outcome for a cancer patient upon treatment with a 4-1BB agonistic agent, for assessing activity of such 4-1BB agonistic agent in a subject, preferably a cancer patient, and for selecting a dose of a 4-1BB agonistic agent for treating a disease, such as cancer. The disclosure also provides methods of treating cancer as well as uses of biomarkers and uses of kits for their detection.