Methods of using anti-CD79b immunoconjugates

Patent metadata

Field	Value
Publication number	US-12016842-B2
Application number	US-202117230861-A
Country	US
Kind code	B2
Filing date	Apr 14, 2021
Priority date	Sep 23, 2014
Publication date	Jun 25, 2024
Grant date	Jun 25, 2024

Abstract

Provided herein are methods of treating B-cell proliferative disorders in particular Follicular Lymphoma and/or Diffuse Large B-Cell Lymphoma using immunoconjugates comprising anti-CD79b antibodies in combination with additional therapeutic agents.

First claim

What is claimed is:

1. A method of treating diffuse large B-cell lymphoma (DLBCL) in an individual, comprising administering to the individual an effective amount of (a) an immunoconjugate comprising an anti-CD79b antibody linked to monomethyl auristatin E (MMAE), (b) obinutuzumab, and (c) a BCL2 inhibitor or a pharmaceutically acceptable salt thereof, wherein the BCL2 inhibitor is venetoclax; and wherein the anti-CD79b antibody comprises: a hypervariable region-H1 (HVR-H1) comprising the amino acid sequence of SEQ ID NO: 21, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 22, an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 23, a hypervariable region-L1 (HVR-L1) comprising the amino acid sequence of SEQ ID NO: 24, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 25, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 26.

2. The method of claim 1 , wherein the immunoconjugate is polatuzumab vedotin.

3. The method of claim 1 , wherein the anti-CD79b antibody comprises (i) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 19, and (ii) a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 20.

4. The method of claim 1 , wherein the anti-CD79b antibody comprises:
(i) a heavy chain comprising the amino acid sequence of SEQ ID NO: 36, and a light chain comprising the amino acid sequence of SEQ ID NO: 35;
(ii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 37, and a light chain comprising the amino acid sequence of SEQ ID NO: 35; or
(iii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 36, and a light chain comprising the amino acid sequence of SEQ ID NO: 38.

5. The method of claim 1 , wherein the anti-CD79b antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 36, and a light chain comprising the amino acid sequence of SEQ ID NO: 35.

6. The method of claim 1 , wherein the immunoconjugate comprises the formula Ab-(L-D)p, wherein:
(a) Ab is the anti-CD79b antibody;
(b) L is a linker;
(c) D is MMAE; and
(d) p is between 1 and 8.

7. The method of claim 6 , wherein the linker comprises (i) a val-cit dipeptide; (ii) a Phe-homoLys dipeptide; or (iii) hydrazine.

8. The method of claim 1 , wherein the immunoconjugate comprises the formula

wherein Ab is the anti-CD79b antibody, Val is valine, Cit is citrulline, and p is between 1 and 8.

9. The method of claim 8 , wherein the immunoconjugate is administered to the individual at a dose of about 1.4 mg/kg or about 1.8 mg/kg.

10. The method of claim 9 , wherein the immunoconjugate is administered to the individual at a dose of about 1.8 mg/kg.

11. The method of claim 1 , wherein obinutuzumab is administered to the individual at a dose of about 1000 mg.

12. The method of claim 1 , wherein the DLBCL is relapsed or refractory DLBCL (RR DLBCL), wherein the immunoconjugate is polatuzumab vedotin, wherein polatuzumab vedotin, obinutuzumab, and venetoclax are administered during an induction phase comprising six 21-day cycles, and wherein
(i) polatuzumab vedotin is administered intravenously on Day 1 of the first 21-day cycle at a dose of about 1.4 mg/kg or about 1.8 mg/kg, venetoclax is administered orally at a dose of 400 mg, 600 mg, or 800 mg once daily on Days 1-21 of the first 21-day cycle, and obinutuzumab is administered intravenously at a dose of about 1000 mg on each of Days 1, 8, and 15 of the first 21-day cycle, and
(ii) polatuzumab vedotin is administered intravenously at a dose of about 1.4 mg/kg or about 1.8 mg/kg on Day 1 of each of the second, third, fourth, fifth, and sixth 21-day cycles, venetoclax is administered orally at a dose of 400 mg, 600 mg, or 800 mg once daily on Days 1-21 of each of the second, third, fourth, fifth, and sixth 21-day cycles, and obinutuzumab is administered intravenously at a dose of about 1000 mg on Day 1 of each of the second, third, fourth, fifth, and sixth 21-day cycles.

13. The method of claim 12 , wherein
(i) venetoclax is administered prior to obinutuzumab and obinutuzumab is administered prior to polatuzumab vedotin on Day 1 of the first 21-day cycle, and venetoclax is administered prior to obinutuzumab on Days 8 and 15 of the first 21-day cycle; and
(ii) venetoclax is administered prior to obinutuzumab and obinutuzumab is administered prior to polatuzumab vedotin on Day 1 of each of the second, third, fourth, fifth, and sixth 21-day cycles.

14. The method of claim 1 , wherein the method is for treating RR DLBCL.

15. The method of claim 12 , wherein venetoclax and obinutuzumab are further administered during a consolidation phase after the sixth 21-day cycle of the induction phase, wherein venetoclax is administered orally at a dose of 400 mg, 600 mg, or 800 mg once per day for 8 months during the consolidation phase, and wherein obinutuzumab is administered intravenously at a dose of about 1000 mg once every two months for 8 months during the consolidation phase.

16. The method of claim 15 , wherein obinutuzumab is administered during the consolidation phase starting on Day 1 of the second month (Month 2) after the sixth 21-day cycle of the induction phase.

17. The method of claim 16 , wherein venetoclax is administered prior to obinutuzumab on Day 1 of each of Month 2, 4, 6, and 8 during the consolidation phase.

18. The method of claim 12 , wherein polatuzumab vedotin is administered intravenously on Day 1 of the first 21-day cycle at a dose of about 1.8 mg/kg, and polatuzumab vedotin is administered intravenously at a dose of about 1.8 mg/kg on Day 1 of each of the second, third, fourth, fifth, and sixth 21-day cycles.

Assignees

• Genentech Inc

Inventors

• Polson Andrew
• Yu Shang-Fan
• Chu Yu-Waye
• Wenger Michael
• Hirata Jamie Harue
• Lu Dan

Classifications

• A61K47/68031

  the drug being an auristatin · CPC title

• A61K31/635

  having a heterocyclic ring, e.g. sulfadiazine · CPC title

• A61K31/454

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title

• A61K31/553

  having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title