GPC3-targeting drug which is administered to patient responsive to GPC3-targeting drug therapy

Patent metadata

Field	Value
Publication number	US-11760807-B2
Application number	US-201515309391-A
Country	US
Kind code	B2
Filing date	May 8, 2015
Priority date	May 8, 2014
Publication date	Sep 19, 2023
Grant date	Sep 19, 2023

Abstract

A method is provided for determining the efficacy of GPC3-targeting drug therapy for cancer in a patient before the start of GPC3-targeting drug therapy or for determining the continuation of GPC3-targeting drug therapy for a patient treated with GPC3-targeting therapy. The method includes determining the number of an immunocyte or an expression level of a molecule expressed on the immunocyte in a biological sample isolated from the patient before the start of GPC3-targeting drug therapy and/or the patient treated with the GPC3-targeting drug therapy, wherein when the number of the immunocyte or the expression level of the molecule expressed on the immunocyte is a predetermined value, the efficacy of the GPC3-targeting drug therapy is determined or the continuation of the GPC3-targeting drug therapy is determined. GPC3-targeting drugs and drug preparations for use according to the disclosed methods are also provided.

First claim

What is claimed is:

1. A method for determining the efficacy of anti-Glypican 3 (GPC3) antibody therapy for GPC3 expressing solid cancer in a patient or determining the continuation of anti-GPC3 antibody therapy for a GPC3 expressing solid cancer patient treated with anti-GPC3 antibody therapy,
said method comprising measuring the number of CD45 + lymphocytes or CD56 − /CD16 + NK cells in a peripheral blood sample isolated from the patient before the start of anti-GPC3 antibody therapy or the patient treated with the anti-GPC3 antibody therapy, wherein when the number of the CD45 + lymphocytes or CD56 − /CD16 + NK cells is a predetermined value, the anti-GPC3 antibody therapy is determined to be effective or the anti-GPC3 antibody therapy is determined to be continued, wherein
(a) when the number measured is the number of CD45 + lymphocytes, the predetermined value is more than a particular value selected from the range from 450 to 3500 cells/μL, or
(b) when the number measured is the number of CD56 − /CD16 + NK cells, the predetermined value is more than a particular value selected from the range from 2 to 30 cells/μL,
said method further comprising administering the anti-GPC3 antibody to the patient for which the efficacy of the anti-GPC3 antibody therapy has been determined or the continuation of the anti-GPC3 antibody therapy has been determined, wherein the anti-GPC3 antibody comprises a member selected from the group consisting of:
(1) a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 50 and a light chain variable region having the amino acid sequence set forth in SEQ ID NO: 51;
(2) a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 50 and a light chain variable region having the amino acid sequence set forth in SEQ ID NO: 66;
(3) a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 67 and a light chain variable region having the amino acid sequence set forth in SEQ ID NO: 68;
(4) a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 69 and a light chain variable region having the amino acid sequence set forth in SEQ ID NO: 70;
(5) a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 71 and a light chain variable region having the amino acid sequence set forth in SEQ ID NO: 72; and
(6) a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 71 and a light chain variable region having the amino acid sequence set forth in SEQ ID NO: 73.

2. The method of claim 1 , wherein the method comprises measuring the number of CD56 − /CD16 + NK cells.

3. The method of claim 1 , wherein the patient has a polymorphism resulting in a homozygous or heterozygous Val at amino acid residue 158 of human FcγRIIIA or a homozygous or heterozygous His at amino acid residue 131 of human FcγRIIA.

4. The method of claim 1 , wherein the GPC3 expressing solid cancer is liver cancer.

5. The method of claim 1 , wherein the anti-GPC3 antibody is administered to achieve a blood trough level of 200 μg/ml or higher in the patient.

6. The method of claim 1 , wherein the anti-GPC3 antibody has antibody-dependent cellular cytotoxicity (ADCC) activity, complement-dependent cytotoxicity (CDC) activity, or ADCC and CDC activity.

7. The method of claim 1 , wherein the anti-GPC3 antibody is conjugated with a cytotoxic substance.

8. The method of claim 1 , wherein the anti-GPC3 antibody is administered to achieve a blood trough level of 230 μg/ml or higher in the patient.

9. The method of claim 1 , wherein the method comprises measuring the number of CD45 + lymphocytes.

10. The method of claim 1 , wherein
(a) when the number measured is the number of CD45 + lymphocytes, the predetermined value is more than a particular value selected from the range from 500 to 3000 cells/μL, or
(b) when the number measured is the number of CD56−/CD16 + NK cells, the predetermined value is more than a particular value selected from the range from 2 to 20 cells/μL.

Assignees

• Chugai Pharmaceutical Co Ltd
• Hoffmann La Roche

Inventors

• Ohtomo Toshihiko
• Tanaka Takayoshi
• Sugitani Yasuo
• Puig Oscar
• Lee Ruey-Min
• Chen Gong
• Belousov Anton
• Chen Ya-Chi
• Reis Bernhard

Classifications

• G01N33/57525

  of the liver or pancreas · CPC title

• G01N33/57595

  involving intracellular compounds · CPC title

• C07K16/303 Primary

  Liver or Pancreas · CPC title

• G01N33/53 Primary

  Immunoassay; Biospecific binding assay; Materials therefor · CPC title

• G01N33/56972

  White blood cells · CPC title