# US 10,869,924 B2 · PD-L1 antagonist combination treatments

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- Number: US 10,869,924 B2
- Document ID: US10869924B2
- Status: Granted
- Kind: B2
- Application number: 15/736,615
- Filed: 2016-06-15
- Published: 2018-06-21
- Granted: 2020-12-22
- Earliest claimed: 2015-06-16
- Assignees: Merck Patent GmbH; Pfizer Inc.
- Applicants: Merck Patent GmbH; Pfizer Inc.
- Inventors: Glen Ian Andrews; Shihao Chen; Alessandra Di Pietro; David Fontana; Zelanna Goldberg; Chia-Yang Lin; Hua Long; Marcella Martignoni; Dimitry Serge Antoine Nuyten; Aron David Thall; Adrian Woolfson
- Web page: https://patentgrep.com/patent/US10869924B2

## CPC

- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 31/4184: condensed with carbocyclic rings, e.g. benzimidazoles
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/706: containing six-membered rings with nitrogen as a ring hetero atom
- A61K 33/243: Platinum; Compounds thereof
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- C07K 16/243: {Colony Stimulating Factors}
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- C07K 16/2887: {against CD20}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The present disclosure describes combination therapies comprising an antagonist of Programmed Death Ligand 1 receptor (PD-L1) and another therapeutic agent, and the use of the combination therapies for the treatment of cancer.

## Claims

### Claim 1

A method for treating a cancer in a human subject comprising administering to the subject a combination therapy which comprises an antagonist of a Programmed Death Ligand 1 protein (PD-L1) and a VEGFR inhibitor, wherein the PD-L1 antagonist is an anti-PD-L1 monoclonal antibody comprising: three CDRs from a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 8, and three CDRs from a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 9, wherein the VEGFR inhibitor is N-methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide or a pharmaceutically acceptable salt thereof and wherein the cancer is renal cell carcinoma.

### Claim 2 (depends on 1)

The method of claim 1, wherein the PD-L1 antagonist is avelumab and the VEGFR inhibitor is axitinib.

### Claim 3 (depends on 2)

The method of claim 2, wherein the PD-L1 antagonist is administered as an initial dose of at least about 5 mg/kg, or about 10 mg/kg; and the VEGFR inhibitor is administered as an initial dose of at least 3 mg or 5 mg.

### Claim 4 (depends on 3)

The method of claim 3, wherein the PD-L1 antagonist is administered about once every two weeks; and the VEGFR inhibitor is administered twice daily.

### Claim 5 (depends on 1)

The method of claim 1, wherein the renal cell carcinoma is advanced renal cell carcinoma.

### Claim 6 (depends on 5)

The method of claim 5, wherein the advanced renal cell carcinoma is previously untreated advanced renal cell carcinoma.

### Claim 7 (depends on 2)

The method of claim 2, wherein the PD-L1 antagonist is administered about once every two weeks.

### Claim 8 (depends on 7)

The method of claim 7, wherein the PD-L1 antagonist is administered at a dose of about 10 mg/kg.

### Claim 9 (depends on 2)

The method of claim 2, wherein the VEGFR inhibitor is administered twice daily.

### Claim 10 (depends on 9)

The method of claim 9, wherein the VEGFR inhibitor is administered at a dose of 5 mg.

### Claim 11 (depends on 2)

The method of claim 2, wherein the PD-L1 antagonist is administered as a 1-hour intravenous infusion.

### Claim 12 (depends on 2)

The method of claim 2, wherein administration of the PD-L1 antagonist and the VEGFR inhibitor is discontinued if unacceptable toxicity occurs.

### Claim 13 (depends on 2)

The method of claim 2, wherein administration of the PD-L1 antagonist and the VEGFR inhibitor is discontinued if disease progression occurs.

### Claim 14

A method for treating renal cell carcinoma in a human subject comprising administering to the subject a combination therapy which comprises avelumab and axitinib, wherein avelumab is administered about once every two weeks, and axitinib is administered twice daily.

### Claim 15 (depends on 14)

The method of claim 14, wherein avelumab is administered at a dose of about 10 mg/kg.

### Claim 16 (depends on 14)

The method of claim 14, wherein axitinib is administered at a dose of 5 mg.

### Claim 17 (depends on 14)

The method of claim 14, wherein avelumab is administered at a dose of about 10 mg/kg, and axitinib is administered at a dose of 5 mg.

### Claim 18 (depends on 14)

The method of claim 14, wherein avelumab is administered as a 1-hour intravenous infusion.

### Claim 19 (depends on 14)

The method of claim 14, wherein the administration of avelumab and axitinib is discontinued if unacceptable toxicity occurs.

### Claim 20 (depends on 14)

The method of claim 14, wherein the administration of avelumab and axitinib is discontinued if disease progression occurs.

### Claim 21

A method for treating renal cell carcinoma in a human subject comprising administering to the subject a combination therapy which comprises avelumab and axitinib, wherein avelumab is administered about once every two weeks as a 1-hour intravenous infusion.

### Claim 22 (depends on 21)

The method of claim 21, wherein avelumab is administered at a dose of about 10 mg/kg.

### Claim 23 (depends on 21)

The method of claim 21, wherein axitinib is administered twice daily.

### Claim 24 (depends on 23)

The method of claim 23, wherein axitinib is administered at a dose of 5 mg.