Methods of using splicing modulators

Patent metadata

Field	Value
Publication number	US-11998544-B2
Application number	US-201917059876-A
Country	US
Kind code	B2
Filing date	May 31, 2019
Priority date	Jun 1, 2018
Publication date	Jun 4, 2024
Grant date	Jun 4, 2024

Abstract

This disclosure relates to methods for the treatment of neoplastic disorders by administering Compound 1, or a pharmaceutically acceptably salt thereof, on its own and/or as part of a conjugate or composition, and inducing production of at least one neoantigen.

First claim

The invention claimed is:

1. A method of treating a subject having or suspected of having a neoplastic disorder, comprising administering to the subject a therapeutically effective amount of Compound 1

or a pharmaceutically acceptable salt thereof, and at least one additional therapy comprising a CTLA4 inhibitor, and wherein the neoplastic disorder is selected from myelodysplastic syndrome, chronic lymphocytic leukemia, acute lymphoblastic leukemia, chronic myelomonocytic leukemia, acute myeloid leukemia, and colon cancer.

2. The method of claim 1 , wherein administration of the Compound 1, or a pharmaceutically acceptable salt thereof, is initiated before, after, or concurrently with administration of the at least one additional therapy.

3. The method of claim 1 , wherein administration of the Compound 1, or a pharmaceutically acceptable salt thereof, and/or the at least one additional therapy is repeated at least once after initial administration.

4. The method of claim 1 ,
wherein the CTLA4 inhibitor is an anti-CTLA4 antibody.

5. The method of claim 1 , wherein the at least one additional therapy comprises at least one, at least two, at least three, at least four, or at least five additional therapies.

6. The method of claim 1 , further comprising detecting one or more neoantigens and/or a T-cell response in the subject after administration of the Compound 1, or a pharmaceutically acceptable salt thereof.

7. The method of claim 6 , further comprising continuing administration of the Compound 1, or a pharmaceutically acceptable salt thereof, after one or more neoantigens and/or a T-cell response is detected.

8. The method of claim 6 , further comprising administering a neoantigen vaccine, wherein the neoantigen vaccine comprises one or more neoantigens detected in the subject after administration of the Compound 1, or a pharmaceutically acceptable salt thereof.

9. The method of claim 1 , wherein the subject has a non-synonymous mutational burden of about 150 mutations or less.

10. The method of claim 1 , wherein the neoplastic disorder is myelodysplastic syndrome.

11. The method of claim 1 , wherein the Compound 1, or a pharmaceutically acceptable salt thereof, is administered as part of a conjugate.

12. The method of claim 4 , wherein the anti-CTLA4 antibody is ipilimumab.

Assignees

• Eisai R&D Man Co Ltd

Inventors

• Pazolli Ermira
• Buonamici Silvia
• Palacino James
• Seiler Michael
• Zhu Ping
• Barry Evan
• Yu Lihua

Classifications

• A61K39/0011

  Cancer antigens · CPC title

• A61K35/17

  Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00) · CPC title

• A61K47/6803

  Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates · CPC title

• C07K16/2818

  against CD28 or CD152 · CPC title

• A61K31/496 Primary

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title