Combined pharmaceutical composition of c-Met kinase inhibitor and anti-PD-L1 antibody
Provided are a combined pharmaceutical composition of an anti-PD-L1 antibody and a c-Met kinase inhibitor, specifically, a combined pharmaceutical composition of an anti-PD-L1 antibody and N-(4-((7-((1-(cyclopentylamino)cyclopropyl)methoxy)-6-methoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and the use of the combined pharmaceutical composition in the treatment of cancers, in particular, gastric cancer or liver cancer.
1 . A combined pharmaceutical composition, comprising:
an anti-PD-L1 antibody and a compound of formula (I) or a pharmaceutically acceptable salt thereof,
wherein the anti-PD-L1 antibody comprises the following amino acid sequences:
a heavy chain CDR1 region consisting of the amino acid sequence set forth in SEQ ID NO:1;
a heavy chain CDR2 region consisting of the amino acid sequence set forth in SEQ ID NO:2;
a heavy chain CDR3 region consisting of the amino acid sequence set forth in SEQ ID NO:3;
a light chain CDR1 region consisting of the amino acid sequence set forth in SEQ ID NO:7;
a light chain CDR2 region consisting of the amino acid sequence set forth in SEQ ID NO:8; and
a light chain CDR3 region consisting of the amino acid sequence set forth in SEQ ID NO:9.
2 . The combined pharmaceutical composition of claim 1 , wherein the anti-PD-L1 antibody and the compound of formula (I) or the pharmaceutically acceptable salt thereof are each in the form of a pharmaceutical composition.
3 . A kit of pharmaceutical compositions for treating cancer, comprising:
(a) a first pharmaceutical composition comprising an anti-PD-L1 antibody of claim 1 as an active ingredient; and
(b) a second pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof of claim 1 as an active ingredient.
4 . A method for treating cancer, comprising:
administering to a subject suffering from cancer a therapeutically effective amount of the combined pharmaceutical composition according to claim 1 .
5 . The method of claim 4 , wherein the anti-PD-L1 antibody is continuously administered at one or more flat doses of about 20 mg to about 2400 mg.
6 . The method of claim 4 , wherein the compound of formula (I) or the pharmaceutically acceptable salt thereof is administered at a dose of 90 mg to 180 mg.
7 . The method of claim 4 , wherein the compound of formula (I) or the pharmaceutically acceptable salt thereof is administered in combination with the anti-PD-L1 antibody in 21-day treatment cycles, and the administration is done by administering by infusion 1200 mg of the anti-PD-L1 antibody over a period of 60±5 min on the first day, and administering 120 mg or 150 mg of the compound of formula (I) or the pharmaceutically acceptable salt thereof once daily over 21 consecutive days.
8 . The method of claim 4 , wherein the cancer is liver cancer or gastric cancer.
9 . The method of claim 8 , wherein the liver cancer is hepatocellular carcinoma.
10 . The method of claim 8 , wherein the gastric cancer is gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.
11 . The combined pharmaceutical composition of claim 1 , wherein the anti-PD-L1 antibody comprises:
the heavy chain variable region set forth in SEQ ID NO:13 and the light chain variable region set forth in SEQ ID NO:15.
12 . The combined pharmaceutical composition of claim 1 , wherein the anti-PD-L1 antibody comprises:
the heavy chain amino acid sequence set forth in SEQ ID NO: 17 and the light chain amino acid sequence set forth in SEQ ID NO: 18.
13 . The method of claim 5 , wherein the anti-PD-L1 antibody is continuously administered at a flat dose of about 1200 mg.
14 . The method of claim 5 , wherein the anti-PD-L1 antibody is administered once every 21 days.
15 . The method of claim 6 , wherein the compound of formula (I) or the pharmaceutically acceptable salt thereof is administered at a dose of 120 mg or 150 mg.
16 . The method of claim 6 , wherein the compound of formula (I) or the pharmaceutically acceptable salt thereof is administered once daily.
17 . A method for treating cancer, comprising:
administering to a subject suffering from cancer a therapeutically effective amount of
(1) a compound of formula (I) or a pharmaceutically acceptable salt thereof,
and
(2) an anti-PD-L1 antibody,
wherein the anti-PD-L1 antibody comprises the following amino acid sequences:
a heavy chain CDR1 region consisting of the amino acid sequence set forth in SEQ ID NO:1;
a heavy chain CDR2 region consisting of the amino acid sequence set forth in SEQ ID NO:2;
a heavy chain CDR3 region consisting of the amino acid sequence set forth in SEQ ID NO:3;
a light chain CDR1 region consisting of the amino acid sequence set forth in SEQ ID NO:7;
a light chain CDR2 region consisting of the amino acid sequence set forth in SEQ ID NO:8; and
a light chain CDR3 region consisting of the amino acid sequence set forth in SEQ ID NO:9,
wherein the anti-PD-L1 antibody is administered at one or more flat doses of about 20 mg to about 2400 mg.
18 . The method of claim 17 , wherein the compound of formula (I) or the pharmaceutically acceptable salt thereof is administered at a dose of 90 mg to 180 mg.
19 . The method of claim 17 , wherein the anti-PD-L1 antibody comprises:
the heavy chain variable region set forth in SEQ ID NO: 13 and the light chain variable region set forth in SEQ ID NO:15.
20 . The method of claim 17 , wherein the anti-PD-L1 antibody comprises:
the heavy chain amino acid sequence set forth in SEQ ID NO: 17 and the light chain amino acid sequence set forth in SEQ ID NO: 18.