Uses of immunoconjugates targeting CD138

Patent metadata

Field	Value
Publication number	US-9289509-B2
Application number	US-77470510-A
Country	US
Kind code	B2
Filing date	May 5, 2010
Priority date	May 6, 2009
Publication date	Mar 22, 2016
Grant date	Mar 22, 2016

Abstract

Disclosed are methods and treatment regimes that include the administration of immunconjugates targeting CD138 to combat diseases. The immunoconjugate is either used as the sole active ingredient, as part of a treatment regime or as part of an anticancer combination.

First claim

What is claimed is:

1. A method for treating a subject with cancer having target cells expressing CD138, wherein said subject has a refractory disease phenotype, comprising:
(i) identifying said subject as not responding, or responding poorly, to treatment with one or more cytotoxic agents, and
(ii) administering to said subject that does not respond, or responds poorly, to treatment with one or more cytotoxic agents an effective amount of an immunoconjugate comprising at least one targeting antibody targeting CD138 expressing cells, and at least one maytansinoid effector molecule, wherein said targeting antibody is functionally attached to said effector molecule to form said immunoconjugate, wherein said immunoconjugate is BT062 or has a light chain having at least about 70% sequence identity with SEQ ID No: 2 and a heavy chain having at least about 70% sequence identity with SEQ ID No: 1, wherein said immunoconjugate comprises residues 24-34 (CDR1), residues 50-56 (CDR2) and residues 89-97 (CDR3) of SEQ ID NO: 2 as well as residues 31-35 (CDR1), residues 51-68 (CDR2) and residues 99-111(CDR3) of SEQ ID No:1.

2. The method of claims 1 , wherein the immunoconjugate is administered to the subject in an amount from 20 mg/m 2 to 200 mg/m 2 or a pharmacokinetic equivalent of 20 mg/m 2 to 200 mg/m 2 when administered in combination with an agent for treating adverse side effects.

3. The method of claim 1 , wherein a maximum concentration of the immunoconjugate in the subject's plasma between 0 to 2 hours after an end of said first intravenous administration is less than 40% of the theoretical maximum concentration for said immunoconjugate.

4. The method of claim 1 , wherein the immunoconjugate is intravenously administered at least four times and a maximum concentration of the immunoconjugate in the subject's plasma between 0 to 2 hours after an end of each of said administrations is less than 55% of the theoretical maximum concentration for said immunoconjugate.

5. The method of claim 1 , wherein said immunoconjugate is administered in a repeated single dose, of not more than about 120 mg/m 2 , an average daily dose of about 400 μg/m 2 to about 6 mg/m 2 , and/or an average weekly dose of about 3 mg/m 2 to about 40 mg/m 2 .

6. The method according to claim 1 , wherein for about 20, 30, 40, 50, 60, 70, 80, 90 100, 120, 140, 160, 180, 190, 200, 210 or more days stable disease is maintained.

7. The method according to claim 1 , wherein for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 treatment cycles each of about three weeks stable disease is maintained.

8. The method of claim 7 , wherein at least stable disease is maintained for 5, 6, 7, 8, 9 or 10 treatment cycles at 20 mg/m 2 .

9. The method of claim 8 , wherein a minor response is observed after up to 8 treatment cycles.

10. The method of claim 1 , wherein said method results in a minor response, a partial response, a very good partial response, a stringent complete response or a complete response durable for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 treatment cycles or more wherein said treatment cycles each comprise about 3 weeks with an administration of said immunoconjugate on day 1 of each said treatment cycle or for 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77 or 82 days, respectively.

11. The method of claim 1 , wherein the immunoconjugate is administered to the subject in an amount from 5 mg/m 2 or 10 m g/m 2 to less than 160 mg/m 2 .

12. The method of claim 3 , wherein said maximum concentration is less than 3 μg/ml for 10 mg/m 2 , less than 8 μg/ml for 20 mg/m 2 , less than 15 μg/ml for 40 mg/m 2 , less than 25 μg/ml for 80 mg/m 2 , less than 30 μg/ml for 120 mg/m 2 .

13. The method of claim 4 , wherein said maximum concentration is less than 14 μg/ml for 20 mg/m 2 , less than 15 μg/ml for 40 mg/m 2 or less than 25 μg/ml for 80 mg/m 2 .

14. The method of claim 1 , wherein said CD138 is, in said subject, expressed on said target cells and on non-target cells, wherein said non-target cells expressing CD138 including epithelial cells, are substantially unaffected.

15. The method of claim 14 , wherein expression level of CD138 on said target and non-target cells expressing CD138 is comparable.

16. The method of claim 14 or 15 , wherein said immunoconjugate is administered to the subject as a single dose, a repeated single dose or in multiple doses in an amount from 5 mg/m 2 to 200 mg/m 2 or a pharmacokinetic equivalent of 5 mg/m 2 to 200 mg/m 2 when administered in combination with an agent for treating adverse side effects and wherein said administering results in a response in said subject, after less than 40, 30, 20, 15, 10, 9, 8, 7, 6, 5 hours.

17. The method of claim 16 , wherein said effective amount is more than 120 mg/m 2 .

18. The method of claim 14 , wherein said effective amount is administered as a single dose, a repeated single dose or in multiple doses.

19. The method of claim 18 , wherein a cmax value after each administration is more than 55% of a theoretical cmax value.

20. The method of claim 14 , wherein said administration results in at least stable disease, a minor response or a partial response in said subject after a first administration.

21. The method of claim 1 , wherein said immunoconjugate comprises nBT062 or a targeting antibody having at least 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity with nBT062.

22. The method of claim 1 , wherein the method consists essentially of administering a pharmaceutical composition comprising said immunoconjugate and a pharmaceutically acceptable carrier, wherein an active ingredient of said composition consists essentially of said immunoconjugate.

23. The method of claim 1 , wherein the immunoconjugate is administered intravenously.

24. The method of claim 23 , wherein the immunoconjugate is administered intravenously in a repeated single dose.

25. The method of claim 1 or 2 , wherein said cancer is selected from the group consisting of renal cell carcinoma, endometrial cancer, cervical cancer, prostate adenocarcinoma, pancreatic carcinoma, gastric cancer, bladder cancer, mammary carcinoma, hepato-carcinoma, colorectal carcinoma, colon carcinoma, squamous cell carcinoma, lung cancer including squamous cell lung carcinoma, non Hodgkin lymphoma, thymus, uterus, urinary or ovarian carcinoma.

26. The method according to claim 1 , wherein the cancer is associated with bone pains and/or bone complications and wherein administration of said immunoconjugate reduces said bone pains and/or bone complications to an acceptable level.

27. The method of claim 1 , wherein the immunoconjugate overcomes the refractory phenotype.

28. A method of treating a patient with cancer having target cells expressing CD138, comprising
(i) identifying said cancer of said patient as being associated with target cells expressing CD138, including multiple myeloma and as not responding, or responding poorly, to treatment with one or more cytotoxic agents including immunomodulators and/or proteasome inhibitors, and
(ii) administering to said patient that does not respond, or responds poorly, to treatment with one or more cytotoxic agents including immunomodulators and/or proteasome inhibitors, intravenously an effective amount of an immunoconjugate comprising nBT062 or a targeting antibody having at least 70%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity with nBT0

Assignees

• Osterroth Frank
• Uherek Christoph
• Bruecher Christoph
• Daelken Benjamin
• Engling Andre
• Haeder Thomas
• Wartenberg-Demand Andrea
• Niemann Gabriele
• Zuber Chantal
• Czeloth Niklas
• Aigner Silke
• Zeng Steffen
• Schulz Gregor
• Biotest Ag
• Immunogen Inc

Inventors

• Osterroth Frank
• Uherek Christoph
• Bruecher Christoph
• Daelken Benjamin
• Engling Andre
• Haeder Thomas
• Wartenberg-Demand Andrea
• Niemann Gabriele
• Zuber Chantal
• Czeloth Niklas
• Aigner Silke
• Zeng Steffen
• Schulz Gregor

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title