Combinations of anti-pd-l1 antibody and mek inhibitor and/or braf inhibitor

A PD-L1, antibody technology, applied in the direction of antibodies, drug combinations, antibody medical components, etc., can solve problems such as functional and weak effector anti-tumor T cell responses

Inactive Publication Date: 2016-06-08
NOVARTIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Thus, although there is a primary antitumor immune response in many cases, the functional, effector antitumor T cell response is usually weak at best

Method used

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  • Combinations of anti-pd-l1 antibody and mek inhibitor and/or braf inhibitor
  • Combinations of anti-pd-l1 antibody and mek inhibitor and/or braf inhibitor
  • Combinations of anti-pd-l1 antibody and mek inhibitor and/or braf inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0369] Embodiment 1-kit composition

[0370] As shown in Tables I and II below, sucrose, microcrystalline cellulose, and compounds A and B of the combination of the present invention were mixed separately in the proportions indicated and granulated with a 10% gelatin solution. The wet granules are sieved, dried, blended with starch, talc and stearic acid, then sieved and compressed into tablets. The kit also includes a vial of anti-PD-L1 antibody as described in Table III.

[0371] Table I

[0372]

[0373] Table I I

[0374]

[0375] Table III

[0376] Anti-PD-L1, 10, 15, 20, 30, 40 or 50ml vials, concentrations 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 mg / ml.

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Abstract

A novel combination comprising the MEK inhibitor N-{3-[3-cyclopropyl-5-(2-fluoro- 4-iodo-phenylamino)6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3- d]pyrimidin-1 -yl]phenyl}acetamide, or a pharmaceutically acceptable salt or solvate thereof, and / or a B-Raf inhibitor, particularly N-{3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1 - dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide or a pharmaceutically acceptable salt thereof, and an anti-PD-L1 antibody; pharmaceutical compositions comprising the same and methods of using such combinations and compositions in the treatment of conditions in which the inhibition of MEK and / or B-Raf and / or neutralizing or inhibiting the interaction between PD-L1 and its receptor, e.g. PD-1, is beneficial, eg. cancer.

Description

technical field [0001] The present invention relates to methods of treating cancer in mammals and to combinations useful in such treatment. In particular, the method involves novel combinations comprising a MEK inhibitor, suitably N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)6, 8-Dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide or A pharmaceutically acceptable salt or solvate thereof, and / or a B-Raf inhibitor, suitably N-{3-[5-(2-amino-4-pyrimidinyl)-2-(1,1-dimethyl ethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide or a pharmaceutically acceptable salt thereof, and an anti-PD-L1 antibody; comprising the combination and methods of using such combinations and compositions to treat disorders, such as cancer, in which inhibiting the interaction of MEK and / or B-Raf and / or PD-L1 with a molecule that binds it, such as PD-1, is benefit. Background technique [0002] Effective treatment of hyperproliferative dise...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/20A61K39/395A61K31/506A61K31/519A61P35/00
CPCA61K39/39558A61K31/506A61K31/519C07K16/2827A61K9/2054A61P35/02A61P35/04A61P35/00A61K2300/00A61K39/3955A61K2039/505
Inventor A·胡斯
Owner NOVARTIS AG
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