Methods of treating cancer using PD-L1 axis binding antagonists and VEGF antagonists
The present invention describes combination treatment comprising a PD-1 axis binding antagonist, chemotherapy and optionally a VEGF antagonist and methods for use thereof, including methods of treating conditions where enhanced immunogenicity is desired such as increasing tumor immunogenicity for the treatment of cancer.
1. A method for treating or delaying progression of colorectal cancer in an individual comprising administering to the individual an effective amount of an anti-PD-L1 antibody, oxaliplatin, leucovorin and 5-FU, wherein the method further comprises administering bevacizumab, wherein the anti-PD-L1 antibody comprises a heavy chain variable region and a light chain variable region, wherein:
(a) the heavy chain variable region comprises an HVR-H1, HVR-H2 and HVR-H3, and wherein:
(i) the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 15;
(ii) the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 16;
(iii) the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 3; and
(b) the light chain variable region comprises an HVR-L1, HVR-L2 and HVR-L3, and wherein:
(iv) the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 17;
(v) the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 18; and
(vi) the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 19.
2. The method of claim 1 , wherein the anti-PD-L1 antibody is a monoclonal antibody.
3. The method of claim 1 , wherein the anti-PD-L1 antibody is an antibody fragment selected from the group consisting of Fab, Fab′-SH, Fv, scFv, and (Fab′) 2 fragments.
4. The method of claim 1 , wherein the anti-PD-L1 antibody is a humanized antibody.
5. The method of claim 1 , wherein the anti-PD-L1 antibody comprises a heavy chain variable region and a light chain variable region, wherein:
(a) the heavy chain variable region amino acid sequence has at least 90% sequence identity to the heavy chain variable region amino acid sequence of SEQ ID NO:20, and
(b) the light chain variable region amino acid sequence has at least 90% sequence identity to the light chain variable region amino acid sequence of SEQ ID NO:21.
6. The method of claim 5 , wherein:
(a) the heavy chain variable region amino acid sequence has at least 95% sequence identity to the heavy chain variable region amino acid sequence of SEQ ID NO:20, and
(b) the light chain variable region amino acid sequence has at least 95% sequence identity to the light chain variable region amino acid sequence of SEQ ID NO:21.
7. The method of claim 6 , wherein:
(a) the heavy chain variable region amino acid sequence has at least 99% sequence identity to the heavy chain variable region amino acid sequence of SEQ ID NO:20, and
(b) the light chain variable region amino acid sequence has at least 99% sequence identity to the light chain variable region amino acid sequence of SEQ ID NO:21.
8. The method of claim 7 , wherein
(a) the heavy chain variable region amino acid sequence has at least 99% sequence identity to the heavy chain variable region amino acid sequence of SEQ ID NO:20, and
(b) the light chain variable region comprises the amino acid sequence of SEQ ID NO:21.
9. The method of claim 8 , wherein the anti-PD-L1 antibody further comprises a human IgG1 constant region.
10. The method of claim 9 , wherein the anti-PD-L1 antibody comprises an effector-less Fc mutation, wherein the effector-less Fc mutation is N297A.