Claims for Patent: 11,701,357

Summary for Patent: 11,701,357

Title:	Treatment of B cell cancers using a combination comprising Btk inhibitors
Abstract:	Disclosed herein is a method for the prevention, delay of progression or treatment of cancer in a subject, comprising administering to the subject in need thereof a Btk inhibitor, particularly, (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a pharmaceutically acceptable salt thereof, in combination with an immune checkpoint inhibitor or a targeted therapy agent. Also, disclosed a pharmaceutical combination comprising a Btk inhibitor, particularly, (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a pharmaceutically acceptable salt thereof, in combination with an immune checkpoint inhibitor, or a targeted therapy agent and the use thereof.
Inventor(s):	Nan Hu, Lai Wang, Jing Song, Tong Zhang, Kang Li, Lusong Luo, Min Wei, Zhiwei Wang, Yunhang Guo
Assignee:	BeiGene Switzerland GmbH
Application Number:	US16/326,467
Patent Claims:	1. A method for the delay of progression or treatment of a B cell cancer in a subject, comprising administering to the subject in need thereof (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide, or a pharmaceutically acceptable salt thereof, at a dose of 320 mg once a day (QD) or 160 mg twice a day (BID) in 28-day cycles, in combination with obinutuzumab administered by three loading doses of 1000 mg weekly followed by 1000 mg on day one of cycles 2-6, wherein the subject is a human. 2. The method of claim 1, wherein the delay of progression or treatment of a B cell cancer in a subject is delay of progression of B cell cancer growth or inhibiting B cell cancer growth in the subject. 3. The method of claim 1, wherein the B-cell cancer is a relapsed or refractory B-cell cancer. 4. The method of claim 3, wherein the relapsed or refractory B-cell cancer is diffuse large B-cell lymphoma (DLBCL), activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL), germinal center B-cell diffuse large B-cell lymphoma (GCB-DLBCL) or non-germinal center B-cell diffuse large B-cell lymphoma (non-GCB DLCBCL). 5. The method of claim 1, wherein the B-cell cancer is a metastasized B-cell cancer. 6. The method of claim 5, wherein the metastasized B-cell cancer is diffuse large B-cell lymphoma (DLBCL), activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL), germinal center B-cell diffuse large B-cell lymphoma (GCB-DLBCL) or non-germinal center B-cell diffuse large B-cell lymphoma (non-GCB DLCBCL). 7. The method of claim 1, wherein the B-cell cancer is chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), non-CLL/SLL lymphoma, follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), Waldenström macroglobulinemia (WM), Hairy cell leukemia (HCL), Burkitt's-like leukemia (BL), B cell prolymphocytic leukemia (B-PLL), diffuse large B cell lymphoma (DLBCL), primary central nervous system lymphoma (PCNSL), secondary central nervous system lymphoma (SCNSL) of breast or testicular origin, multiple myeloma, or a combination of two or more thereof. 8. The method of claim 7, wherein the DLBCL is activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL), germinal center B-cell diffuse large B-cell lymphoma (GCB-DLBCL), non-germinal center B-cell diffuse large B-cell lymphoma (Non-GCB DLBCL), or diffuse large B-cell lymphoma (DLBCL) with undetermined subtype. 9. The method of claim 7, wherein the B-cell cancer is follicular lymphoma (FL). 10. The method of claim 9, wherein the FL is relapsed or refractory. 11. The method of claim 9, wherein the obinutuzumab is administered at a dose of 1,000 mg intravenously on days 1, 8, and 15 of cycle 1, followed by 1,000 mg intravenously on day 1 of each cycle of cycles 2 to 6; and each cycle is 28 days. 12. The method of claim 11, wherein the FL is relapsed or refractory. 13. The method of claim 9, wherein the (S)-7-(1-acryloylpiperidin-4-yl)-2-4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide, or a pharmaceutically acceptable salt thereof, is administered orally, and the obinutuzumab is administered intravenously. 14. The method of claim 13, wherein the (S)-7-(1-acryloylpiperidin-4-yl)-2-4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide, or a pharmaceutically acceptable salt thereof, is administered at a dose of 160 mg twice a day (BID). 15. The method of claim 14, wherein the FL is relapsed or refractory. 16. The method of claim 13, wherein the (S)-7-(1-acryloylpiperidin-4-yl)-2-4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide, or a pharmaceutically acceptable salt thereof, is administered at a dose of 320 mg once a day (QD). 17. The method of claim 16, wherein the FL is relapsed or refractory. 18. The method of claim 1, wherein the (S)-7-(1-acryloylpiperidin-4-yl)-2-4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide, or a pharmaceutically acceptable salt thereof, is administered orally, and the obinutuzumab is administered intravenously. 19. The method of claim 11, wherein the (S)-7-(1-acryloylpiperidin-4-yl)-2-4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide, or a pharmaceutically acceptable salt thereof, is administered orally.