Therapeutic and diagnostic methods for cancer

• US 20190315868A1
• Filed: 02/07/2019
• Published: 10/17/2019
• Est. Priority Date: 08/08/2016
• Status: Active Application

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Klein, Christian, Deak, Laura Codarri
• Application Number:
  US16/270,334
• Publication Number:
  US 20190315868A1
• Time in Patent Office: Days
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/70532 B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 16/2827 against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

The present invention provides therapeutic and diagnostic methods and compositions for cancer and for enhancing immune function in an individual having cancer. The invention provides methods of treatment, methods for determining whether an individual suffering from a cancer is responding to treatment comprising a PD-1 axis binding antagonist, predicting responsiveness of an individual suffering from a cancer to treatment comprising a PD-1 axis binding antagonist, and methods of selecting a therapy for an individual suffering from cancer.

Claims

1-53. -53. (canceled)

54. A method for treating an individual suffering from a cancer, the method comprising administering an effective amount of a PD-1 axis binding antagonist to the individual, wherein the ratio between Granzyme B⁺ CD4⁺ T cells and FOXP3⁺ CD4⁺ T cells in a blood sample obtained from the individual has been determined to be 1 or greater.

62. The method of claim 54, wherein the cancer is selected from the group consisting of bladder cancer, squamous cell cancer, lung cancer including small-cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), adenocarcinoma of the lung, squamous carcinoma of the lung, cancer of the peritoneum, hepatocellular cancer, gastric or stomach cancer including gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, hepatoma, breast cancer, colon cancer, rectal cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, renal cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma, anal carcinoma, penile carcinoma, Merkel cell cancer, testicular cancer, esophageal cancer, tumors of the biliary tract, head and neck cancer and hematological malignancies.

63. The method of claim 54, wherein the PD-1 axis binding antagonist is a PD-L1 binding antagonist.

64. The method of claim 63, wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to PD-1.

65. The method of claim 63, wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to both PD-1 and B7-1.

66. The method of claim 63, wherein the PD-L1 binding antagonist is an antibody.

67. The method of claim 66, wherein the antibody is selected from the group consisting of atezolizumab (MPDL3280A), YW243.55.S70, MDX-1105, MEDI4736 (durvalumab), and MSB0010718C (avelumab).

68. The method of claim 67, wherein the antibody comprises a heavy chain comprising HVR-H1 sequence of SEQ ID NO:

19, HVR-H2 sequence of SEQ ID NO;

20, and HVR-H3 sequence of SEQ ID NO;

21; and

a light chain comprising HVR-L1 sequence of SEQ ID NO;

22, HVR-L2 sequence of SEQ ID NO;

23, and HVR-L3 sequence of SEQ ID NO;

24.

69. The method of claim 68, wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

25 and a light chain variable region comprising the amino acid sequence of SEQ ID NO;

4.

70. The method of claim 54, wherein the PD-1 axis binding antagonist is a PD-1 binding antagonist.

71. The method of claim 70, wherein the PD-1 binding antagonist inhibits the binding of PD-1 to PD-L1.

72. The method of claim 71, wherein the PD-1 binding antagonist inhibits the binding of PD-1 to both PD-Li and PD-L2.

73. The method of claim 70, wherein the PD-1 binding antagonist is an antibody.

74. The method of claim 73, wherein the antibody is selected from the group consisting of:

MDX-1106 (nivolumab), MK-3475 (pembrolizumab), MEDI-0680 (AMP-514), PDR001, REGN2810, and BGB-108.

75. The method of claim 70, wherein the PD-1 binding antagonist is an Fc-fusion protein.

76. The method of claim 75, wherein the Fc-fusion protein is AMP-224.

55-61. -61. (canceled)