# US 12,214,036 B2 · Combination therapy comprising AXL/MER and PD-1/PD-L1 inhibitors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,214,036 B2 - Document ID: US12214036B2 - Status: Granted - Kind: B2 - Application number: 17/193,631 - Filed: 2021-03-05 - Published: 2021-09-09 - Granted: 2025-02-04 - Earliest claimed: 2020-03-06 - Assignees: Incyte Corporation - Applicants: Incyte Corporation - Inventors: Jonathan Rios-Doria; Holly K. Koblish - Web page: https://patentgrep.com/patent/US12214036B2 ## CPC - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61K 31/53: having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) - A61P 35/00: Antineoplastic agents - C07K 16/2818: {against CD28 or CD152} - A61K 2039/505: {comprising antibodies} - A61K 2039/54: {characterised by the route of administration} - A61K 2039/545: {characterised by the dose, timing or administration schedule} - C07K 2317/52: Constant or Fc region; Isotype - 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 relates to methods of treating cancer by administering a compound, which is an AXL/MER kinase inhibitor, in combination with an antibody, or an antibody fragment thereof, that binds to PD-1. ## Claims ### Claim 1 A method of treating cancer in a patient, comprising administering to said patient: (i) Compound 1, having the structure: or a pharmaceutically acceptable salt thereof; and (ii) an antibody, or an antigen-binding fragment thereof, that binds to human PD-1, wherein the antibody, or the antigen-binding fragment thereof comprises a variable heavy (VH) domain and a variable light (VL) domain, wherein the VH domain comprises the amino acid sequence set forth in SEQ ID NO:4 and the VL domain comprises the amino acid sequence set forth in SEQ ID NO:5; wherein the cancer is colorectal cancer. ### Claim 2 (depends on 1) The method of claim 1, wherein Compound 1 and the antibody are administered simultaneously. ### Claim 3 (depends on 1) The method of claim 1, wherein Compound 1 and the antibody are administered sequentially. ### Claim 4 (depends on 1) The method of claim 1, wherein Compound 1 is administered orally. ### Claim 5 (depends on 1) The method of claim 1, wherein the antibody or antigen-binding fragment is administered via intravenous administration. ### Claim 6 (depends on 1) The method of claim 1, wherein the antibody or antigen-binding fragment is administered at a dose of 375 mg once every 3 weeks. ### Claim 7 (depends on 1) The method of claim 1, wherein the antibody or antigen-binding fragment is administered at a dose of 500 mg once every 4 weeks. ### Claim 8 (depends on 1) The method of claim 1, wherein the antibody or antigen-binding fragment is administered at a dose of 750 mg once every 4 weeks. ### Claim 9 (depends on 1) The method of claim 1, wherein: (a) the antibody comprises an Fc Region and a Hinge Domain; (b) the Fc Region and the Hinge Domain are of the IgG4 type; and (c) the Hinge Domain comprises a stabilizing mutation. ### Claim 10 (depends on 1) The method of claim 1, wherein the antibody comprises a heavy chain and wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:2. ### Claim 11 (depends on 1) The method of claim 1, wherein the antibody comprises a light chain and wherein the light chain comprises the amino acid sequence set forth in SEQ ID NO:3. ### Claim 12 (depends on 1) The method of claim 1, wherein the antibody comprises a heavy chain and a light chain, and wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 2 and the light chain comprises the amino acid sequence set forth in SEQ ID NO:3. ### Claim 13 (depends on 1) The method of claim 1, wherein the antibody comprises an Fc Region that is of the IgG1 type. ### Claim 14 (depends on 1) The method of claim 1, wherein the antibody comprises a heavy chain and wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:13. ### Claim 15 (depends on 1) The method of claim 1, wherein the antibody comprises a light chain and a heavy chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 13 and the light chain comprises the amino acid sequence set forth in SEQ ID NO:3. ### Claim 16 (depends on 1) The method of claim 1, wherein the antibody is a humanized antibody. ### Claim 17 (depends on 1) The method of claim 1, wherein: a) Compound 1 and the antibody are administered sequentially; b) Compound 1 is administered orally; and c) the antibody or antigen-binding fragment is administered via intravenous administration.