Methods of treating cancers using PD-1 axis binding antagonists and taxanes

• US 10,570,213 B2
• Filed: 05/27/2016
• Issued: 02/25/2020
• Est. Priority Date: 12/17/2013
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Kim, Jeong, Cheung, Jeanne
• Primary Examiner(s): Ouspenski, Ilia I
• Application Number:
  US15/167,125
• Publication Number:
  US 20160257752A1
• Time in Patent Office: 1,369 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/282 Platinum compounds
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/643 Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2809 against the T-cell receptor (TcR)-CD3 complex
• 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 16/30 from tumour cells
• CPC Class Codes: C07K 16/3015 Breast
• CPC Class Codes: C07K 16/3023 : Lung
• CPC Class Codes: C07K 16/303 : Liver or Pancreas
• CPC Class Codes: C07K 16/3038 : Kidney, bladder
• CPC Class Codes: C07K 16/3069 : Reproductive system, e.g. ovaria, uterus, testes, prostate
• CPC Class Codes: C07K 16/32 : against translation products of oncogenes
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 : multispecific
• CPC Class Codes: C07K 2317/41 : Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/52 : Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/524 : CH2 domain
• CPC Class Codes: C07K 2317/526 : CH3 domain
• CPC Class Codes: C07K 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 : Stability, e.g. half-life, pH, temperature or enzyme-resistance

Abstract

The invention provides methods and compositions for treating cancer and for enhancing immune function in an individual having cancer. The methods comprise administering a PD-1 axis binding antagonist and a taxane.

Claims

1. A method for treating or delaying progression of non-squamous non-small cell lung cancer (NSCLC) in an individual comprising administering to the individual 1200 mg of an anti-PD-L1 antibody every three weeks, the anti-PD-L1 antibody comprising 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, wherein the antibody is administered in combination with a taxane selected from paclitaxel or nab-paclitaxel and carboplatin.

2. The method of claim 1, wherein the anti-PD-L1 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.

3. The method of claim 1 or 2, wherein the taxane is nab-paclitaxel.

4. The method of claim 1 or 2, wherein the taxane is paclitaxel.

9. The method of claim 1 or 5, wherein the non-squamous NSCLC is metastatic non-squamous NSCLC.

10. The method of claim 1 or 5, wherein cancer cells in the individual express PD-L1.

11. The method of claim 1 or 5, wherein the treatment results in a response in the individual.

12. The method of claim 11, wherein the response is a complete response.

13. The method of claim 11, wherein the response is a sustained response after cessation of the treatment.

14. The method of claim 1, wherein the taxane and/or the carboplatin is administered before the anti-PD-L1 antibody, simultaneous with the anti-PD-L1 antibody, or after the anti-PD-L1 antibody.

15. The method of claim 14, wherein the taxane and/or the carboplatin is administered before the anti-PD-L1 antibody.

16. The method of claim 14, wherein the taxane and/or the carboplatin is administered simultaneously with the anti-PD-L1 antibody.

17. The method of claim 14, wherein the taxane and/or the carboplatin is administered after the anti-PD-L1 antibody.

18. The method of claim 1, wherein the anti-PD-L1 antibody, the taxane, and/or the carboplatin is administered intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, or intranasally.

19. The method of claim 18, wherein the anti-PD-L1 antibody, the taxane, and the carboplatin are administered intravenously.

26. The method of claim 1 or 5, wherein the taxane is paclitaxel, and the paclitaxel is administered at a dose of 200 mg/m² intravenously every three weeks.

27. The method of claim 1 or 5, wherein the taxane is nab-paclitaxel, and the nab-paclitaxel is administered at a dose of 100 mg/m² intravenously every three weeks.

28. The method of claim 1 or 5, wherein the carboplatin is administered with a target area under the curve (AUC) of 6 mg/ml intravenously every three weeks.

5. A method for treating or delaying progression of non-squamous NSCLC in an individual comprising administering to the individual 1200 mg of an anti-PD-L1 antibody every three weeks, the anti-PD-L1 antibody comprising 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, wherein the anti-PD-L1 antibody is administered in combination with bevacizumab, a taxane selected from paclitaxel or nab-paclitaxel, and carboplatin.

6. The method of claim 5, wherein the anti-PD-L1 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.

7. The method of claim 5 or 6, wherein the taxane is paclitaxel.

8. The method of claim 5 or 6, wherein the taxane is nab-paclitaxel.

20. The method of claim 5, wherein the bevacizumab, the taxane, and/or the carboplatin is administered before the anti-PD-L1 antibody, simultaneous with the anti-PD-L1 antibody, or after the anti-PD-L1 antibody.

21. The method of claim 20, wherein the bevacizumab, the taxane, and/or the carboplatin is administered before the anti-PD-L1 antibody.

22. The method of claim 20, wherein the bevacizumab, the taxane, and/or the carboplatin is administered simultaneously with the anti-PD-L1 antibody.

23. The method of claim 20, wherein the bevacizumab, the taxane, and/or the carboplatin is administered after the anti-PD-L1 antibody.

24. The method of claim 5, wherein the anti-PD-L1 antibody, the bevacizumab, the taxane, and/or the carboplatin is administered intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, or intranasally.

25. The method of claim 24, wherein the anti-PD-L1 antibody, the bevacizumab, the taxane, and the carboplatin are administered intravenously.

29. A method for treating or delaying progression of metastatic non-squamous NSCLC in an individual comprising administering to the individual 1200 mg of an anti-PD-L1 antibody by intravenous infusion every three weeks, the anti-PD-L1 antibody comprising 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, wherein the anti-PD-L1 antibody is administered in combination with bevacizumab, paclitaxel, and carboplatin.

30. The method of claim 29, wherein the anti-PD-L1 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.

31. The method of claim 29, wherein the anti-PD-L1 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:

32 and a light chain comprising the amino acid sequence of SEQ ID NO;

33.