Use of bispecific antigen-binding molecules that bind MUC16 and CD3 in combination with 4-1BB co-stimulation
Provided herein are method of treating cancer using bispecific antigen-binding molecules that bind to Mucin 16 (MUC16) and CD3. According to certain embodiments, the antibodies useful herein bind human MUC16 with high affinity and bind CD3 to induce human T cell proliferation. According to certain embodiments, bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3, and a second antigen-binding molecule that specifically binds human MUC16 are particularly useful herein. In certain embodiments, the bispecific antigen-binding molecules in combination with an anti-4-1BB agonist are capable of inhibiting the growth of tumors expressing MUC16, for example, ovarian tumors. The bispecific antigen-binding molecules in combination with an anti-4-1BB agonist are useful for the treatment of diseases and disorders in which an upregulated or induced targeted immune response is desired and/or therapeutically beneficial, for example, in the treatment of various cancers.
1. A method of treating a cancer that expresses MUC16 or inhibiting the growth of a MUC16-expressing tumor comprising administering to a subject in need thereof a therapeutically effective amount each of (a) an anti-CD3/anti-MUC16 bispecific antigen-binding molecule; and (b) a 4-1BB agonist.
2. The method of claim 1 , wherein the cancer is selected from the group consisting of breast cancer, ovarian cancer, corneal cancer, pancreatic cancer, endometrial cancer, fallopian tube cancer, mesothelioma, non-small cell lung cancer, intrahepatic cholangiocarcinoma-mass forming type, uterine cancer, cervical cancer, gastric cancer, or colorectal carcinoma.
3. The method of claim 2 , wherein the cancer is ovarian cancer.
4. The method of claim 2 , wherein the cancer is breast cancer.
5. The method of claim 1 , wherein the anti-CD3/anti-MUC16 bispecific antibody and the 4-1BB agonist are administered separately.
6. The method of claim 1 , wherein the anti-CD3/anti-MUC16 bispecific antibody and the 4-1BB agonist are co-administered.
7. The method of claim 1 , wherein the anti-CD3/anti-MUC16 bispecific antibody is administered prior to, concurrent with or after the 4-1BB agonist.
8. The method of claim 7 , wherein the anti-CD3/anti-MUC16 bispecific antibody is administered prior to the 4-1BB agonist.
9. The method of claim 7 , wherein the anti-CD3/anti-MUC16 bispecific antibody is administered the same day as the 4-1BB agonist.
10. The method of claim 1 , wherein the anti-CD3/anti-MUC16 bispecific antibody is administered in combination with the 4-1BB agonist.
11. The method of claim 1 , wherein the 4-1BB agonist is selected from a small molecule or an antibody.
12. The method of claim 11 , wherein the 4-1BB agonist is an antibody selected from the group consisting of urelumab and utomilumab.
13. The method of claim 1 , wherein the bispecific antigen-binding molecule comprises a first antigen-binding domain that specifically binds CD3 and comprises a HCVR-1 amino acid sequence of SEQ ID NO: 2, a second antigen-binding domain that specifically binds MUC16 and comprises a HCVR-2 amino acid sequence of SEQ ID NO: 1, and a common light chain variable region (LCVR) amino acid sequence of SEQ ID NO: 3.
14. The method of claim 1 , wherein the tumor volume is decreased relative to tumor volume in a subject administered the anti-CD3/anti-MUC16 bispecific antigen-binding molecule in the absence of a 4-1BB agonist.
15. The method of claim 1 , wherein tumor free survival time is increased in the subject relative to tumor free survival time in a subject administered the anti-CD3/anti-MUC16 bispecific antigen-binding molecule in the absence of a 4-1BB agonist.
16. The method of claim 15 , wherein the increase in tumor free survival time occurs without weight loss in the subject.
17. The method of claim 1 , wherein subsequent exposure to tumor cells elicits a memory response in the subject treated with the anti-CD3/anti-MUC16 bispecific antigen-binding molecule in the presence of a 4-1BB agonist.