Combination of a CBP/p300 bromodomain inhibitor and a KRAS inhibitor for the treatment of cancer
Inventors
FLÜCKIGER-MANGUAL, Stefanie • Gruber, Dorothea • Bohnacker, Thomas • Schwill, Martin • SCHMITZ-ROHMER, Debora • Fabritius, Charles-Henry • Laudato, Sara
Assignees
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Publication Number
US-12472179-B2
Publication Date
2025-11-18
Expiration Date
Abstract
The present invention is inter alia concerned with (i) a combination of a CBP/p300 bromodomain inhibitor and a KRAS inhibitor for use in the treatment of a patient suffering from cancer, wherein the cancer exhibits an oncogenic alteration in the KRAS; (ii) a kit comprising (a) a pharmaceutical dosage form comprising a CBP/p300 bromodomain inhibitor and (b) a pharmaceutical dosage form comprising a KRAS inhibitor, and (iii) a pharmaceutical dosage form comprising a CBP/p300 bromodomain inhibitor and a KRAS inhibitor.
Core Innovation
The invention concerns a method of treating a patient suffering from cancer exhibiting an oncogenic alteration in KRAS, where the oncogenic alteration is caused by at least one base mutation in the KRAS gene resulting in the amino acid substitution G12C in KRAS. The method comprises administering a combination of a CBP/p300 bromodomain inhibitor and a KRAS inhibitor to the patient, and is directed to KRAS G12C-driven cancers.
The disclosed approach further describes pharmaceutical dosage forms and kits that include a CBP/p300 bromodomain inhibitor and a KRAS G12C inhibitor. The CBP/p300 bromodomain inhibitor and the KRAS inhibitor are provided as respective pharmaceutical dosage forms in a kit, and a pharmaceutical dosage form comprises both inhibitor types.
The document also describes CREBBP bromodomain bound to a compound identified as compound 00004 and the use of bromodomain binding assays. The functional studies describe effects on cell proliferation and resistance, including long-term culture contexts showing that CBP/p300 bromodomain inhibitors do not strongly affect proliferation alone but prevent resistance to covalent KRAS G12C inhibitors.
Claims Coverage
The independent claims cover three categories: a combination treatment method for KRAS G12C cancer, a kit containing two pharmaceutical dosage forms, and a pharmaceutical dosage form comprising both inhibitor types. Across the independents, the inventive features center on KRAS G12C patient selection, co-administration of a CBP/p300 bromodomain inhibitor with a KRAS inhibitor, and product formats that include the two inhibitor types.
Treating KRAS G12C cancer with a CBP/p300 bromodomain inhibitor and a KRAS inhibitor
Administering a combination of a CBP/p300 bromodomain inhibitor and a KRAS inhibitor to a patient suffering from cancer that exhibits an oncogenic alteration in KRAS caused by at least one base mutation resulting in the amino acid substitution G12C in KRAS.
Kit with a CBP/p300 bromodomain inhibitor dosage form and a KRAS G12C inhibitor dosage form
A kit comprising a pharmaceutical dosage form comprising a CBP/p300 bromodomain inhibitor and a pharmaceutical dosage form comprising a KRAS G12C inhibitor.
Pharmaceutical dosage form with a CBP/p300 bromodomain inhibitor and a KRAS G12C inhibitor
A pharmaceutical dosage form comprising a CBP/p300 bromodomain inhibitor and a KRAS G12C inhibitor.
The claim set constrains the invention to KRAS G12C cancers and centers co-usage of CBP/p300 bromodomain inhibition with KRAS inhibition. It is covered as a patient treatment method and as combined pharmaceutical product formats containing the two inhibitor components.
Stated Advantages
Deeper/longer-lasting proliferation inhibition.
Mitigates the decline in KRAS-inhibitor effect over time attributed to resistance.
Prevents resistance to the KRAS inhibitor.
Increased therapeutic efficacy versus KRAS inhibitor monotherapy.
Extended therapeutic effect duration versus KRAS inhibitor monotherapy.
Documented Applications
Treatment of a patient suffering from cancer with a KRAS oncogenic alteration caused by a KRAS base mutation resulting in the KRAS G12C amino-acid substitution, using a combination of a CBP/p300 bromodomain inhibitor and a KRAS inhibitor.
Use of a kit comprising a pharmaceutical dosage form including a CBP/p300 bromodomain inhibitor and a pharmaceutical dosage form including a KRAS G12C inhibitor.
Use of a pharmaceutical dosage form comprising a CBP/p300 bromodomain inhibitor and a KRAS G12C inhibitor.
Treatment of cancer selected from lung cancer, colorectal cancer, or pancreatic cancer using the combination approach for KRAS G12C-driven cancers.
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