JPWO2019222252A5 - - Google Patents

Claims (20)

A pharmaceutical composition comprising a first polypeptide and a protein comprising a second polypeptide for treating advanced non-small cell lung cancer (NSCLC) or inhibiting tumor growth in untreated patients in need . A dose of at least 500 mg of protein, including the first polypeptide and the second polypeptide, is administered to the patient.
The first polypeptide is (a) at least one variable region of the heavy chain of an antibody that binds to human protein program death ligand 1 (PD-L1); and (b) human transforming growth factor β receptor II ( Contains a fragment thereof capable of binding to TGFβRII) or transforming growth factor β (TGFβ).
The second polypeptide comprises at least one variable region of the light chain of the antibody that binds PD-L1.
A pharmaceutical composition in which the heavy chain of the first polypeptide and the light chain of the second polypeptide, when combined, form an antigen binding site that binds to PD-L1. The pharmaceutical composition according to claim 1, wherein the first polypeptide comprises the amino acid sequences of SEQ ID NOs: 35, 36 and 37 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 1. The pharmaceutical composition according to claim 1, wherein the first polypeptide comprises the amino acid sequence of SEQ ID NO: 3, and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 1. The pharmaceutical composition according to any one of claims 1 to 3, wherein the dose is 500 mg to 2400 mg, 1200 mg to 3000 mg, 1200 mg, or 2400 mg . The pharmaceutical composition according to any one of claims 1 to 4, wherein the dose is administered once every two weeks or once every three weeks. The pharmaceutical composition according to claim 4 , wherein the dose is 1200 mg and is administered once every two weeks. The pharmaceutical composition according to claim 4 , wherein the dose is 2400 mg and is administered once every 3 weeks. The pharmaceutical composition according to any one of claims 1 to 7 , wherein the advanced NSCLC shows a squamous epithelial or non-squamous epithelial histology. The pharmaceutical composition according to any one of claims 1 to 8 , wherein the cancer exhibits high PD-L1 expression. The patient according to any one of claims 1 to 9 , wherein the patient does not have a mutation selected from the group consisting of an EGFR sensitized mutation, an ALK translocation, a ROS1 mutation, and a BRAF V600E mutation. Pharmaceutical composition . The pharmaceutical composition according to any one of claims 1 to 10 , wherein administration of the protein results in a disease response or improved survival of the patient. The pharmaceutical composition of claim 11 , wherein the disease response is a disease of complete remission, partial remission, or stability. The pharmaceutical composition according to claim 11 , wherein the survival time is progression-free survival (PFS). The pharmaceutical composition according to any one of claims 1 to 13 , wherein the protein is administered by intravenous administration. The pharmaceutical composition according to claim 14 , wherein the intravenous administration is carried out by a filled bag containing the preparation containing the protein, a filled pen, or a filled syringe. 15. The pharmaceutical composition of claim 15 , wherein the bag is connected to a conduit comprising a tube and / or a needle. A method for treating advanced non-small cell lung cancer (NSCLC) or inhibiting tumor growth in an untreated cancer patient in need , comprising 500 mg to 3000 mg of protein comprising a first polypeptide and a second polypeptide. An intravenous drug delivery formulation for use in, wherein the protein is administered to the patient ;
The first polypeptide is (a) at least one variable region of the heavy chain of an antibody that binds to human protein program death ligand 1 (PD-L1); and (b) human transforming growth factor β receptor II ( Contains a fragment thereof capable of binding to TGFβRII) or transforming growth factor β (TGFβ).
The second polypeptide comprises at least one variable region of the light chain of the antibody that binds PD-L1.
A drug delivery preparation for intravenous injection, wherein the heavy chain of the first polypeptide and the light chain of the second polypeptide, when combined, form an antigen-binding site that binds to PD-L1. The drug delivery preparation for intravenous injection according to claim 17, which comprises 1200 mg of the protein. A drug delivery device for use in methods for treating advanced non-small cell lung cancer (NSCLC) or inhibiting tumor growth in untreated cancer patients in need, wherein the device is a first polypeptide. And a formulation containing 500 mg to 3000 mg of protein, including a second polypeptide;
The first polypeptide is (a) at least one variable region of the heavy chain of an antibody that binds to human protein program death ligand 1 (PD-L1); and (b) human transforming growth factor β receptor II ( Contains a fragment thereof capable of binding to TGFβRII) or transforming growth factor β (TGFβ).
The second polypeptide comprises at least one variable region of the light chain of the antibody that binds PD-L1.
A drug delivery device in which the heavy chain of the first polypeptide and the light chain of the second polypeptide, when combined, form an antigen binding site that binds to PD-L1. 19. The drug delivery device of claim 19, comprising 1200 mg of the protein .