Combination therapies
Inventors
Aranda, Ruth Wei • Christensen, James Gail • Engstrom, Lars Daniel • Hallin, Jill • Olson, Peter
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12208099-B2
Publication Date
2025-01-28
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 Raf family kinase 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 describes combination therapy for treating non-small cell lung cancer in a subject in need thereof. The method administers a therapeutically effective amount of Raf family kinase inhibitor Lifirafenib (BGB-283) together with a KRAS G12C inhibitor of a specified formula, or a pharmaceutically acceptable salt thereof. The Raf family kinase inhibitor acts to synergistically increase sensitivity to the KRAS G12C inhibitor and thereby inhibit KRas G12C activity in non-small cell lung cancer cells.
The invention addresses the problem of treating KRAS G12C-associated cancers, including non-small cell lung cancer, by improving the outcome of KRAS G12C inhibitor treatment. The described combination is stated to increase sensitivity and inhibitory activity against KRAS G12C-expressing cancers, with outcomes expressed as improved overall survival and progression-free survival. The document also describes tumor regression, tumor growth inhibition, and increased stable disease duration relative to treatment with the KRAS G12C inhibitor alone.
The invention further characterizes synergy using synergy assessment models and synergy scores, and includes evaluation frameworks comparing combinations to KRAS G12C inhibitor monotherapy. The document references inhibitor activity endpoints involving KRAS G12C and downstream signaling, including covalent modification of KRAS G12C and phosphorylated ERK, and relates these endpoints to sensitivity against KRAS G12C-expressing cancer cells. The described combination is also supported by in vivo xenograft results showing substantially greater tumor regression than either agent alone.
Claims Coverage
The provided claim set includes three independent claims that collectively cover treating non-small cell lung cancer in a subject with Lifirafenib (BGB-283) plus a KRAS G12C inhibitor, inhibiting KRas G12C activity in a non-small cell lung cancer cell by contacting the cell with the same combination, and providing a kit containing separate pharmaceutical compositions of Lifirafenib (BGB-283) and the KRAS G12C inhibitor for treating KRAS G12C non-small cell lung cancer. Across the independent claims, the main inventive requirement is that the Raf family kinase inhibitor synergistically increases sensitivity to the KRAS G12C inhibitor and thereby inhibits KRas G12C activity.
Non-small cell lung cancer treatment using Lifirafenib plus a KRAS G12C inhibitor
Administering to a subject in need thereof a therapeutically effective amount of a combination of Raf family kinase inhibitor Lifirafenib (BGB-283) and a KRAS G12C inhibitor of formula or a pharmaceutically acceptable salt thereof.
Inhibiting KRas G12C activity by synergistic sensitivity increase
Contacting a non-small cell lung cancer cell in which inhibition of KRas G12C activity is desired with an effective amount of Raf family kinase inhibitor Lifirafenib (BGB-283) and a KRAS G12C inhibitor of formula or a pharmaceutically acceptable salt thereof, wherein the Raf family kinase inhibitor synergistically increases the sensitivity of the non-small cell lung cancer cell to the KRAS G12C inhibitor.
Treatment kit with separate pharmaceutical compositions for Raf family kinase inhibitor and KRAS G12C inhibitor
A kit comprising a pharmaceutical composition comprising Raf family kinase inhibitor Lifirafenib (BGB-283) and a pharmaceutical composition comprising a KRAS G12C inhibitor of formula or a pharmaceutically acceptable salt thereof for treating a KRAS G12C non-small cell lung cancer in a subject.
The independent claims cover treating KRAS G12C non-small cell lung cancer using a combination that includes Lifirafenib (BGB-283) and a KRAS G12C inhibitor of a specified formula, or salts, and they require, in the cell-contact claim, that Lifirafenib synergistically increases sensitivity to the KRAS G12C inhibitor to enable inhibition of KRas G12C activity. A kit claim further covers providing the two pharmaceutical actives as separate compositions for treating the same indication.
Stated Advantages
Improved overall survival duration versus treatment with only the KRAS G12C inhibitor.
Improved progression-free survival duration versus treatment with only the KRAS G12C inhibitor.
Increased tumor growth regression versus treatment with only the KRAS G12C inhibitor.
Increased tumor growth inhibition versus treatment with only the KRAS G12C inhibitor.
Increased stable disease duration versus treatment with only the KRAS G12C inhibitor.
Synergistically increases sensitivity of non-small cell lung cancer cells to the KRAS G12C inhibitor.
Substantially greater tumor regression than either agent alone.
Documented Applications
Treating non-small cell lung cancer in a subject in need thereof using a combination of Lifirafenib (BGB-283) and a KRAS G12C inhibitor, or a pharmaceutically acceptable salt.
Inhibiting KRas G12C activity in a non-small cell lung cancer cell by contacting the cell with Lifirafenib (BGB-283) and a KRAS G12C inhibitor, or a pharmaceutically acceptable salt.
Providing a kit comprising pharmaceutical compositions of Lifirafenib (BGB-283) and a KRAS G12C inhibitor for treating KRAS G12C non-small cell lung cancer in a subject.
Interested in licensing this patent?