Combination of a car t cell therapy and an immunomodulatory compound for treatment of lymphoma

A method of treating a lymphoma, the method comprising administering to a subject having a cancer that is a lymphoma a combination therapy comprising:

• (i) a T cell therapy comprising a dose of engineered cells comprising T cells expressing a chimeric antigen receptor (CAR) that binds cluster of differentiation 19 (CD19), wherein the T cell therapy is administered on Day 1 of the combination therapy;
• and
• (ii) a compound that is (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione or a pharmaceutically acceptable salt thereof.

A method of treating a cancer expressing CD19, the method comprising administering to a subject having a cancer expressing CD19 a compound that is (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione or a pharmaceutically acceptable salt thereof, wherein:

• the compound is administered in a combination therapy with a T cell therapy comprising a dose of engineered cells comprising T cells expressing a chimeric antigen receptor (CAR) directed against the cancer, wherein the T cell therapy is administered on Day 1 of the combination therapy, and the administration of the compound is initiated subsequently to the administration of the T cell therapy.

A method of treating a lymphoma, the method comprising administering to a subject having a cancer that is a lymphoma a compound that is (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione or a pharmaceutically acceptable salt thereof, wherein:

• the compound is administered in a combination therapy with a T cell therapy comprising a dose of engineered cells comprising T cells expressing a chimeric antigen receptor (CAR) that binds cluster of differentiation 19 (CD19), wherein the T cell therapy is administered on Day 1 of the combination therapy, and the administration of the compound is initiated subsequently to the administration of the T cell therapy.

A method of treating a lymphoma, the method comprising administering to a subject having a cancer that is a lymphoma a combination therapy comprising:

• (i) a T cell therapy comprising a dose of engineered cells comprising T cells expressing a chimeric antigen receptor (CAR) that binds cluster of differentiation 19 (CD19), wherein the T cell therapy is administered on Day 1 of the combination therapy;
• and
• (ii) a compound that is (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione or a pharmaceutically acceptable salt thereof, wherein the compound is administered as a plurality of intermittent doses administered no more than once weekly, wherein each dose is between at or about 0.1 mg and at or about 0.6 mg, inclusive, wherein the administration of the compound is initiated between Day 1 and Day 29, inclusive, of the combination therapy.

A method of treating a lymphoma, the method comprising administering to a subject having a cancer that is a lymphoma a compound that is (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione or a pharmaceutically acceptable salt thereof, wherein:

• the compound is administered in a combination therapy with a T cell therapy comprising a dose of engineered cells comprising T cells expressing a chimeric antigen receptor (CAR) that binds cluster of differentiation 19 (CD19), wherein the T cell therapy is administered on Day 1 of the combination therapy;
• and
• the compound is administered as a plurality of intermittent doses administered no more than once weekly, wherein each dose is between at or about 0.1 mg and at or about 0.6 mg, inclusive, and wherein the administration of the compound is initiated between Day 1 and Day 29, inclusive, of the combination therapy.

A method of treating a lymphoma, the method comprising administering to a subject having a cancer that is a lymphoma a compound that is (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione or a pharmaceutically acceptable salt thereof, wherein:

• the compound is administered in a combination therapy with a T cell therapy comprising a dose of engineered cells comprising T cells expressing a chimeric antigen receptor (CAR) that binds cluster of differentiation 19 (CD19), wherein the T cell therapy is administered on Day 1 of the combination therapy;
• and
• the compound is administered as a plurality of intermittent doses administered once every seven days (Q7D) and is administered on Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85, wherein each dose is 0.3 mg.

A method of treating a lymphoma, the method comprising administering to a subject having a cancer that is a lymphoma a compound that is (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione or a pharmaceutically acceptable salt thereof, wherein:

• the compound is administered in a combination therapy with a T cell therapy comprising a dose of engineered cells comprising T cells expressing a chimeric antigen receptor (CAR) that binds cluster of differentiation 19 (CD19), wherein the T cell therapy is administered on Day 1 of the combination therapy;
• and
• the compound is administered as a plurality of intermittent doses administered once every seven days (Q7D) and is administered on Days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85, wherein each dose is 0.3 mg.

A method of treating a lymphoma, the method comprising administering to a subject having a cancer that is a lymphoma a compound that is (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione or a pharmaceutically acceptable salt thereof, wherein:

• the compound is administered in a combination therapy with a T cell therapy comprising a dose of engineered cells comprising T cells expressing a chimeric antigen receptor (CAR) that binds cluster of differentiation 19 (CD19), wherein the T cell therapy is administered on Day 1 of the combination therapy;
• and
• the compound is administered as a plurality of intermittent doses administered once every seven days (Q7D) and is administered on Days 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85, wherein each dose is 0.3 mg.

A method of treating a lymphoma, the method comprising administering to a subject having a cancer that is a lymphoma a compound that is (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione or a pharmaceutically acceptable salt thereof, wherein:

• the compound is administered in a combination therapy with a T cell therapy comprising a dose of engineered cells comprising T cells expressing a chimeric antigen receptor (CAR) that binds cluster of differentiation 19 (CD19), wherein the T cell therapy is administered on Day 1 of the combination therapy;
• and
• the compound is administered as a plurality of intermittent doses administered once every seven days (Q7D) and is administered on Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85, wherein each dose is 0.4 mg.

A method of treating a lymphoma, the method comprising administering to a subject having a cancer that is a lymphoma a compound that is (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione or a pharmaceutically acceptable salt thereof, wherein:

• the compound is administered in a combination therapy with a T cell therapy comprising a dose of engineered cells comprising T cells expressing a chimeric antigen receptor (CAR) that binds cluster of differentiation 19 (CD19), wherein the T cell therapy is administered on Day 1 of the combination therapy;
• and
• the compound is administered as a plurality of intermittent doses administered once every 14 days (Q14D) and is administered on Days 8, 22, 36, 50, 64, and 78, wherein each dose is 0.3 mg.

A method of treating a lymphoma, the method comprising administering to a subject having a cancer that is a lymphoma a compound that is (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione or a pharmaceutically acceptable salt thereof, wherein:

• the compound is administered in a combination therapy with a T cell therapy comprising a dose of engineered cells comprising T cells expressing a chimeric antigen receptor (CAR) that binds cluster of differentiation 19 (CD19), wherein the T cell therapy is administered on Day 1 of the combination therapy;
• and
• the compound is administered as a plurality of intermittent doses administered once every seven days (Q7D) and is administered on Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85, wherein each dose is 0.2 mg.

A method of treating a lymphoma, the method comprising administering to a subject having a cancer that is a lymphoma a compound that is (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione or a pharmaceutically acceptable salt thereof, wherein:

• the compound is administered in a combination therapy with a T cell therapy comprising a dose of engineered cells comprising T cells expressing a chimeric antigen receptor (CAR) that binds cluster of differentiation 19 (CD19), wherein the T cell therapy is administered on Day 1 of the combination therapy;
• and
• the compound is administered as a plurality of intermittent doses administered once every seven days (Q7D) and is administered on Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85, wherein each dose is 0.6 mg.