	US 11,951,166 B2
	Combination of regorafenib and PD-1/PD-L1(2) inhibitors for treating cancer
Sabine Hoff, Potsdam (DE); Lars Rose, Berlin (DE); Dieter Zopf, Berlin (DE); Fabian Kiessling, Aachen (DE); Wiltrud Lederle, Aachen (DE); and Dennis Doleschel, Aachen (DE)
Assigned to BAYER AKTIENGESELLSCHAFT, Leverkusen (DE)
Appl. No. 16/617,642
Filed by BAYER AKTIENGESELLSCHAFT, Leverkusen (DE)
PCT Filed May 25, 2018, PCT No. PCT/EP2018/063785 § 371(c)(1), (2) Date Nov. 27, 2019, PCT Pub. No. WO2018/219807, PCT Pub. Date Dec. 6, 2018.
Claims priority of application No. 17174169.7 (EP), filed on Jun. 2, 2017.
Prior Publication US 2020/0179354 A1, Jun. 11, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/395 (2006.01); A61K 9/00 (2006.01); A61K 31/44 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01)

CPC A61K 39/3955 (2013.01) [A61K 9/0019 (2013.01); A61K 31/44 (2013.01); A61P 35/00 (2018.01); A61K 2039/505 (2013.01)]

27 Claims

1. 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.