Combination therapies
AssigneeMirati Therapeutics, Inc.
InventorsDavid Briere, James Gail Christensen, Peter Olson
Life of this patent
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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 an agent that blocks Programmed Death-1 receptor (PD-1) and Programmed Death Ligand-1 (PD-L1) signaling and a KRAS G12C inhibitor of Formula (I), Formula I-A or Formula I-B, kits comprising the compositions and methods of use therefor.
Claims43
A method of treating a KRas G12C-associated cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a combination of a PD-1/PD-L1 inhibitor selected from the group consisting of nivolumab, pembrolizumab, cemiplimab, tislelizumab, atezolizumab, avelumab, and durvalumab, and a compound of formula:
- or a pharmaceutically acceptable salt thereof.
A pharmaceutical composition comprising a therapeutically effective amount of a PD-1/PD-L1 inhibitor selected from the group consisting of nivolumab, pembrolizumab, cemiplimab, tislelizumab, atezolizumab, avelumab, and durvalumab and a compound of formula:
- or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
A method of treating a KRas G12C-associated cancer in a subject in need thereof, wherein the KRas G12C-associated cancer is resistant to treatment with a PD-1/PD-L1 inhibitor, comprising administering to the subject a therapeutically effective amount of a combination of a PD-1/PD-L1 inhibitor selected from the group consisting of nivolumab, pembrolizumab, cemiplimab, tislelizumab, atezolizumab, avelumab, and durvalumab or a pharmaceutical composition thereof, and a compound of formula:
- or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.
A method for treating a KRas G12C-associated cancer and determined to have previously developed resistance to treatment with a PD-1/PD-L1 inhibitor that include administering to the subject a therapeutically effective amount of a combination of a PD-1/PD-L1 inhibitor selected from the group consisting of nivolumab, pembrolizumab, cemiplimab, tislelizumab, atezolizumab, avelumab, and durvalumab or a pharmaceutical composition thereof, and a compound of formula:
- or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.
A method for suppressing resistance to treatment with a PD-1/PD-L1 inhibitor in a subject having a KRas G12C-associated cancer that include administering to the subject a therapeutically effective amount of a combination of a PD-1/PD-L1 inhibitor selected from the group consisting of nivolumab, pembrolizumab, cemiplimab, tislelizumab, atezolizumab, avelumab, and durvalumab, or a pharmaceutical composition thereof, and a compound of formula:
- or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.
A method of treating a subject identified or diagnosed as having a KRAS G12C-associated cancer that include (a) detecting resistance of the KRas G12C-associated cancer in the subject to treatment with a PD-1/PD-L1 inhibitor that was previously administered to the patient;
- and (b) after (a), administering to the subject a therapeutically effective amount of a combination of a PD-1/PD-L1 inhibitor selected from the group consisting of nivolumab, pembrolizumab, cemiplimab, tislelizumab, atezolizumab, avelumab, and durvalumab, or a pharmaceutical composition thereof, and a compound of formula:
- or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.
A method of treating a subject identified or diagnosed as having a KRas G12C-associated cancer and determined to have previously developed resistance to treatment with a KRAS G12C inhibitor that include administering to the subject a therapeutically effective amount of a combination of a PD-1/PD-L1 inhibitor selected from the group consisting of nivolumab, pembrolizumab, cemiplimab, tislelizumab, atezolizumab, avelumab, and durvalumab, or a pharmaceutical composition thereof, and a compound of formula:
- or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.
A method of treating a subject identified or diagnosed as having a KRas G12C-associated cancer, comprising (a) administering a KRAS G12C inhibitor as monotherapy until disease progression, and (b) after (a), administering to the subject a therapeutically effective amount of a combination of a PD-1/PD-L1 inhibitor selected from the group consisting of nivolumab, pembrolizumab, cemiplimab, tislelizumab, atezolizumab, avelumab, and durvalumab, or a pharmaceutical composition thereof, and a compound of formula:
- or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.
A kit comprising:
- a) a pharmaceutical composition comprising a PD-1/PD-L1 inhibitor selected from the group consisting of nivolumab, pembrolizumab, cemiplimab, tislelizumab, atezolizumab, avelumab, and durvalumab, and b) a pharmaceutical composition comprising a compound of formula:
- or a pharmaceutically acceptable salt thereof, for treating a KRas G12C cancer in a subject.
Dependencies are inferred from the claim text.