Methods For Treating Cancer Using Combination Therapies

An in vitro assay for identifying a ligand conjugate suitable for co-administration to a patient with a thiol inhibitor, the assay comprising:

• a) adding the ligand conjugate to the culture medium of a first sample of cultured cells, wherein the ligand conjugate comprises a disulfide linkage;
• b) adding the thiol inhibitor to the culture medium of the first sample of cultured cells to provide a test sample;
• c) adding the ligand conjugate to the culture medium of a second sample of cultured cells to provide a control sample;
• d) measuring the non-ligand-specific activity of the ligand conjugate or the nonspecific uptake of the drug in the test sample;
• e) measuring the non-ligand-specific activity of the ligand conjugate or the nonspecific uptake of the drug in the control sample;
• and
• f) determining that the ligand conjugate is suitable for co-administration to the patient with the thiol inhibitor if the non-ligand-specific activity of the ligand conjugate and/or the nonspecific uptake of the drug are decreased in the test sample relative to the control sample,
• wherein the ligand conjugate is of the formula BLDX, wherein B is a cell surface receptor targeting ligand, D is an independently selected drug, x is an integer selected from 1, 2, 3, 4 and 5;
• and L is a releasable polyvalent linker comprising a thiol reactive linkage;
• or a pharmaceutically acceptable salt thereof,
• wherein B is a PSMA binding ligand, and
• wherein the PSMA binding ligand is