Administration of SUMO-activating enzyme inhibitor and anti-CD20 antibodies
The present disclosure provides methods, pharmaceutical compositions, and kits for treating cancer or autoimmune disease in patients in need thereof. The methods comprise administering to a patient in need a small ubiquitin-like modifier (SUMO) activating enzyme (SAE) inhibitor, such as [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxy-cyclopentyl]methyl sulfamate (Compound I-263a) or a pharmaceutically acceptable salt, in combination with one or more anti-CD20 antibodies. Also provided are medicaments for use in treating cancer or autoimmune disease.
1. A method of treating a disorder, wherein the disorder is lymphoma or leukemia, comprising administering to a patient in need of said treating a combination of [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate (Compound I-263a) or a pharmaceutically acceptable salt thereof, and an anti-CD20 antibody.
2. The method of claim 1 , wherein the anti-CD20 antibody is a Type I anti-CD20 antibody.
3. The method of claim 1 , wherein the anti-CD20 antibody is selected from the group consisting of ublituximab, ofatumumab, ocrelizumab, veltuzumab, obinutuzumab, AME-133v, ocaratuzumab, PRO131921, tositumomab, ibritumomab-tiuxetan, hA20, BLX-301, Reditux, PRO70769, and rituximab.
4. The method of claim 1 , wherein the anti-CD20 antibody is rituximab.
5. The method of claim 1 , wherein the [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate (Compound I-263a) or a pharmaceutically acceptable salt thereof, is administered orally, intravenously, or subcutaneously.
6. The method of claim 1 , wherein the [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl) pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate (Compound I-263a) or a pharmaceutically acceptable salt thereof, is administered by intravenous infusion.
7. The method of claim 1 , wherein the disorder is CD20 positive chronic lymphocytic leukemia or CD20 positive non-Hodgkin's lymphoma.
8. The method of claim 1 , wherein the disorder is follicular lymphoma (FL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), Diffuse large B-cell lymphoma (DLBCL), or Burkitt lymphoma.
9. The method of claim 1 , wherein the [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate (Compound I-263a) or a pharmaceutically acceptable salt thereof, is administered once every two weeks, once every week, twice a week, three times a week, or daily.
10. The method of claim 1 , wherein the [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate (Compound I-263a) or a pharmaceutically acceptable salt thereof, is administered on days 1 and 8 of a 21 day cycle or on days 1, 4, 8, and 11 of a 21 day cycle.
11. The method of claim 1 , wherein the anti-CD20 antibody is administered once every two weeks, once every week, twice a week, three times a week, or daily.
12. The method of claim 11 , wherein the anti-CD20 antibody is administered once every week.
13. The method of claim 1 , wherein the anti-CD20 antibody is administered on Day 1 of a treatment cycle.
14. The method of claim 13 , wherein the treatment cycle is 21 days or 28 days.
15. The method of claim 1 , wherein the [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate (Compound I-263a) or a pharmaceutically acceptable salt thereof, and the anti-CD20 antibody are administered simultaneously once every eight weeks, once every four weeks, once every two weeks, once every week, twice a week, three times a week, daily, on days 1 and 8 of a 21 day cycle, or on days 1, 4, 8, and 11 of a 21 day cycle.
16. The method of claim 1 , wherein:
the [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate (Compound I-263a) or a pharmaceutically acceptable salt thereof, is administered orally once every two weeks, once every week, twice a week, three times a week, daily, on days 1 and 8 of a 21 day cycle, or on days 1, 4, 8, and 11 of a 21 day cycle; and
the anti-CD20 antibody is separately administered once every eight weeks, once every four weeks, once every two weeks, once every week, twice a week, three times a week, daily, on day 1 of a 21 day cycle, or once every week for three doses followed by administration on day 1 of one or more subsequent 21 day cycles.
17. The method of claim 1 , wherein the [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate (Compound I-263a) or a pharmaceutically acceptable salt thereof, is administered on days 1, 4, 8, and 11 of a 21 day cycle.
18. The method of claim 9 , wherein the [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate (Compound I-263a), or a pharmaceutically acceptable salt thereof, is administered once every week.
19. The method of claim 18 , wherein the [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate (Compound I-263a) or a pharmaceutically acceptable salt thereof, is administered in an amount of 60 mg on each day of dosing.
20. The method of claim 18 , wherein the [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate (Compound I-263a) or a pharmaceutically acceptable salt thereof, is administered in an amount of 120 mg on each day of dosing.
21. The method of claim 1 , wherein:
the anti-CD20 antibody is rituximab;
the [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate (Compound I-263a) or a pharmaceutically acceptable salt thereof, is administered in an amount of 60 mg or 120 mg on each day of dosing;
the rituximab is administered in an amount of 375 mg/m 2 on each day of dosing; and
the [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate (Compound I-263a) or a pharmaceutically acceptable salt thereof, is administered once every week for one or more treatment cycles.