# US 2018/0021431 A1 · Methods of treating cancer using pd-1 axis binding antagonists and mek inhibitors

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- Number: US 2018/0021431 A1
- Document ID: US20180021431A1
- Status: Published application
- Kind: A1
- Application number: 15/635,920
- Filed: 2017-06-28
- Published: 2018-01-25
- Earliest claimed: 2011-08-01
- Assignees: Genentech, Inc.
- Applicants: Genentech, Inc.
- Inventors: Heather MAECKER; Bryan IRVING
- Web page: https://patentgrep.com/patent/US20180021431A1

## CPC

- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 31/4184: condensed with carbocyclic rings, e.g. benzimidazoles
- A61K 31/4355: the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
- A61K 31/44: Non condensed pyridines; Hydrogenated derivatives thereof
- A61K 31/4523: containing further heterocyclic ring systems
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 47/62: the modifying agent being a protein, peptide or polyamino acid
- A61K 47/64: Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65)
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/04: Immunostimulants
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- C07K 16/3046: {Stomach, Intestines}
- C07K 16/3053: {Skin, nerves, brain}
- A61K 2039/505: {comprising antibodies}
- 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 invention describes combination treatment comprising a PD-1 axis binding antagonist and a MEK inhibitor 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.

## Claims

### Claim 1

A method for treating or delaying progression of colorectal cancer or melanoma in an individual comprising administering to the individual an effective amount of an anti-PD-1 antibody and a MEK inhibitor, wherein the MEK inhibitor is selected from the group consisting of G02442104, G-38963, G02443714, G00039805 and GDC-0973, or a pharmaceutically acceptable salt or solvate thereof.

### Claim 2

(canceled)

### Claim 3

(canceled)

### Claim 4 (depends on 1)

The method of claim 1, wherein the anti-PD-1 antibody inhibits the binding of PD-1 to its ligand binding partners.

### Claim 5 (depends on 4)

The method of claim 4, wherein the anti-PD-1 antibody inhibits the binding of PD-1 to PD-L1.

### Claim 6 (depends on 4)

The method of claim 4, wherein the anti-PD-1 antibody inhibits the binding of PD-1 to PD-L2.

### Claim 7 (depends on 4)

The method of claim 4 wherein the anti-PD-1 antibody inhibits the binding of PD-1 to both PD-L1 and PD-L2.

### Claim 8

(canceled)

### Claim 9 (depends on 1)

The method of claim 1, wherein the anti-PD-1 antibody is MDX-1106.

### Claim 10 (depends on 1)

The method of claim 1, wherein the anti-PD-1 antibody is Merck 3745.

### Claim at position 11

11-29: (canceled)

### Claim 30 (depends on 1)

The method of claim 1, wherein the MEK inhibitor is G02443714, G02442104 or G00039805, or a pharmaceutically acceptable salt or solvate thereof.

### Claim 31 (depends on 1)

The method of claim 1, wherein the colorectal cancer or melanoma contains a BRAF V600E mutation.

### Claim 32 (depends on 1)

The method of claim 1, wherein the colorectal cancer or melanoma contains a BRAF wildtype.

### Claim 33 (depends on 1)

The method of claim 1, wherein the colorectal cancer contains a KRAS wildtype.

### Claim 34 (depends on 1)

The method of claim 1, wherein the colorectal cancer contains an activating KRAS mutation.

### Claim 35 (depends on 1)

The method of claim 1, wherein the treatment results in a sustained response in the individual after cessation of the treatment.

### Claim 36 (depends on 1)

The method of claim 1, wherein the MEK inhibitor is administered continuously.

### Claim 37 (depends on 1)

The method of claim 1, wherein the MEK inhibitor is administered intermittently.

### Claim 38 (depends on 1)

The method of claim 1, wherein the MEK inhibitor is administered before the anti-PD-1 antibody.

### Claim 39 (depends on 1)

The method of claim 1, wherein the MEK inhibitor is administered simultaneous with the anti-PD-1 antibody t.

### Claim 40 (depends on 1)

The method of claim 1, wherein the MEK inhibitor is administered after the anti-PD-1 antibody.

### Claim at position 23

41-72: (canceled)

### Claim 73 (depends on 1)

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

### Claim at position 25

74-79: (canceled)

### Claim 80 (depends on 1)

The method of claim 1, wherein the MEK inhibitor is G02442104, or a pharmaceutically acceptable salt or solvate thereof.

### Claim 81 (depends on 1)

The method of claim 1, wherein the MEK inhibitor is G-38963, or a pharmaceutically acceptable salt or solvate thereof.

### Claim 82 (depends on 1)

The method of claim 1, wherein the MEK inhibitor is G02443714, or a pharmaceutically acceptable salt or solvate thereof.

### Claim 83 (depends on 1)

The method of claim 1, wherein the MEK inhibitor is G00039805, or a pharmaceutically acceptable salt or solvate thereof.

### Claim 84 (depends on 1)

The method of claim 1, wherein the MEK inhibitor is GDC-0973, or a pharmaceutically acceptable salt or solvate thereof.

### Claim 85

A method for treating or delaying progression of colorectal cancer in an individual comprising administering to the individual an effective amount of GDC-0973, or a pharmaceutically acceptable salt thereof, and an effective amount of an anti-PD-1 antibody.

### Claim 86 (depends on 85)

The method of claim 85, wherein the anti-PD-1 antibody is MDX-1106.

### Claim 87 (depends on 85)

The method of claim 85, wherein the anti-PD1 antibody is Merck 3745.

### Claim 88

A method for treating or delaying progression of melanoma in an individual comprising administering to the individual an effective amount of GDC-0973, or a pharmaceutically acceptable salt thereof, and an effective amount of an anti-PD-1 antibody.

### Claim 89 (depends on 88)

The method of claim 88, wherein the anti-PD-1 antibody is MDX-1106.

### Claim 90 (depends on 88)

The method of claim 88, wherein the anti-PDL1 antibody is Merck 3745.