Combination of regorafenib and PD-1/PD-L1(2) inhibitors for treating cancer
AssigneeBayer Aktiengesellschaft
InventorsSabine Hoff, Lars Rose, Dieter Zopf, Fabian Kiessling, Wiltrud Lederle, Dennis Doleschel
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Abstract
The present invention relates to pharmaceutical compositions and combinations comprising regorafenib or its hydrate, solvate, metabolite or pharmaceutically acceptable salt or a polymorph thereof and a PD-1/PD-L1(2) inhibitor for treating, preventing or managing diseases and conditions including hyperproliferative disorders such as cancer in humans and other mammals.
Claims27
A method of treating cancer in a subject in need thereof comprising administering effective amounts of chemotherapeutic agents, wherein the chemotherapeutic agents are separate from one another and consist of
- a) regorafenib or its hydrate, solvate, metabolite, pharmaceutically acceptable salt, or a polymorph thereof and
- b) an anti-PD-1 antibody that inhibits PD-1,
- wherein, the regorafenib metabolite is selected from the group consisting of:
- 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl] carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide I-oxide,
- 4- [4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-(hydroxymethyl)pyridine-2-carboxamide,
- 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]pyridine-2-carboxamide and
- 4-[4-({[4-chloro-3(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]pyridine-2-carboxamide I-oxide.
A method of treating hyper-proliferative disorders in a subject in need thereof comprising administering chemotherapeutic agents, wherein said chemotherapeutic agents are separate from one another and consist of effective amounts of
- 1) regorafenib and/or its monohydrate in the form of a tablet and
- 2) pembrolizumab
- wherein the hyper-proliferative disorders are selected from the group consisting of hepatic cell cancer, colorectal cancer and gastrointestinal stromal tumors (GIST).
A pharmaceutical combination comprising chemotherapeutic agents, wherein the chemotherapeutic agents are separate from one another and consist of
- a) regorafenib or its hydrate, solvate, metabolite, pharmaceutically acceptable salt, or a polymorph thereof and
- b) an anti-PD-1 antibody that inhibits PD-1,
- wherein the regorafenib metabolite is selected from the group consisting of:
- 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl] carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide I-oxide,
- 4-[4({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-(hydroxymethyl)pyridine-2-carboxamide,
- 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]pyridine-2-carboxamide and
- 4-[4-({[4-chloro-3(trifluoromethyl)phenyl] carbamoyl}amino)-3-fluorophenoxy]pyridine-2-carboxamide I-oxide.
A pharmaceutical combination comprising chemotherapeutic agents, wherein the chemotherapeutic agents are separate from one another and consist of
- a) regorafenib and/or its monohydrate and b) an anti-PD-1 antibody that inhibits PD-1.
A pharmaceutical combination comprising chemotherapeutic agents, wherein the chemotherapeutic agents are separate from one another and consist of
- a) regorafenib and/or its monohydrate and
- b) pembrolizumab.
Dependencies are inferred from the claim text.