Combination therapies
Inventors
Christensen, James Gail • Engstrom, Lars Daniel • Aranda, Ruth Wei • Hallin, Jill • Olson, Peter
Assignees
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Publication Number
US-12336995-B2
Publication Date
2025-06-24
Expiration Date
Abstract
The present invention relates to combination therapies for treating KRas G12C cancers. In particular, the present invention relates to methods of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a combination of a pan ErbB family inhibitor and a KRAS G12C inhibitor of Formula (I), Formula (I-A) or Formula (I-B), pharmaceutical compositions comprising a therapeutically effective amounts of the inhibitors, kits comprising the compositions and methods of use therefor.
Core Innovation
The invention provides a combination cancer therapy targeting KRAS G12C-associated cancers by administering a therapeutically effective amount of cetuximab together with a therapeutically effective amount of a KRAS G12C inhibitor of formula, including subformulas I-A and I-B, or a pharmaceutically acceptable salt thereof. The combination is described in the context of treating cancer in a subject in need thereof.
The KRAS G12C inhibitors are covalent (irreversible) binders that bind to the G12C cysteine sulfhydryl. The therapy co-administers a pan ErbB family inhibitor with the KRAS G12C inhibitor, where the pan ErbB family inhibitor is described to include EGFR inhibitors, HER2 inhibitors, and EGFR/HER2 antibody combinations, with cetuximab specifically identified among the examples.
The described therapeutic approach claims synergistic increases in KRAS G12C inhibitor potency and improved clinical outcomes versus KRAS G12C inhibitor alone, including overall survival, progression-free survival, tumor regression or tumor growth inhibition, and stable disease duration. The document further describes methods for determining KRAS G12C status and for timing/scheduling co-administration, and it includes composition and kit concepts for the combination therapy.
Claims Coverage
The provided independent claims cover three main inventive subject-matter categories: treatment of colorectal cancer with a cetuximab plus KRAS G12C inhibitor combination, and kit formats comprising cetuximab and the KRAS G12C inhibitor components. Across these independent claims, the inventive features primarily focus on the combination of cetuximab with a formula-defined KRAS G12C inhibitor and the kit composition that includes both therapeutics for colorectal cancer treatment.
Combination therapy with cetuximab and formula-defined KRAS G12C inhibitor for colorectal cancer
A method of treating colorectal cancer in a subject in need thereof by administering a combination therapy comprising a therapeutically effective amount of cetuximab and a therapeutically effective amount of a KRAS G12C inhibitor of formula, or a pharmaceutically acceptable salt thereof.
Combination therapy with cetuximab and formula-defined KRAS G12C inhibitor for colorectal cancer with improved clinical outcomes
A method of treating colorectal cancer in a subject in need thereof by administering a combination therapy comprising a therapeutically effective amount of cetuximab and a therapeutically effective amount of a KRAS G12C inhibitor of formula, including expected clinical outcome improvements relative to treatment with only the KRAS G12C inhibitor.
Kit comprising cetuximab and a formula-defined KRAS G12C inhibitor composition
A kit comprising a pharmaceutical composition comprising cetuximab and a pharmaceutical composition comprising a KRAS G12C inhibitor of formula, or a pharmaceutically acceptable salt thereof, for treating colorectal cancer in a subject.
Kit comprising cetuximab and separate formula-defined KRAS G12C inhibitor composition
A kit comprising a pharmaceutical composition comprising cetuximab and a pharmaceutical composition comprising a KRAS G12C inhibitor of formula for treating colorectal cancer in a subject.
Across the independent claims, the core claimed coverage is the administration or provision of a combination that includes cetuximab together with a KRAS G12C inhibitor defined by a specified formula, or a pharmaceutically acceptable salt, for treating colorectal cancer, including kit formats with the relevant pharmaceutical compositions.
Stated Advantages
Improved overall survival versus treatment with only the KRAS G12C inhibitor.
Improved progression-free survival versus treatment with only the KRAS G12C inhibitor.
Tumor growth inhibition and/or tumor regression versus treatment with only the KRAS G12C inhibitor.
Increased duration of stable disease versus treatment with only the KRAS G12C inhibitor.
Synergistic increases in KRAS G12C inhibitor potency versus KRAS G12C inhibitor alone.
Documented Applications
Treating colorectal cancer in a subject using a combination therapy comprising cetuximab and a KRAS G12C inhibitor of a specified formula, or a pharmaceutically acceptable salt.
Using kit formats containing pharmaceutical compositions comprising cetuximab and a KRAS G12C inhibitor of a specified formula, or a pharmaceutically acceptable salt, for treating colorectal cancer in a subject.
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