JPWO2021022256A5 - - Google Patents

Claims (28)

1. A pharmaceutical composition for use in combination with one or more chemotherapeutic agents in the treatment of a solid tumor in a subject, comprising an antibody that binds to human galectin-9 (anti-Gal9 antibody) , wherein
said anti-Gal9 antibody has the same heavy chain complementarity determining regions (CDRs) and the same light chain CDRs as antibody G9.2-17;
A pharmaceutical composition for use wherein one or more of said chemotherapeutic agents comprises gemcitabine, paclitaxel or a combination thereof. The pharmaceutical composition for use according to claim 1, wherein said solid tumor is a metastatic solid tumor. 3. The pharmaceutical composition for use according to claim 1 or 2, wherein said solid tumor is pancreatic ductal adenocarcinoma (PDAC). For use according to any one of claims 1 to 3, wherein said anti-Gal9 antibody is administered to said subject by intravenous injection at a dose of about 0.5 mg/kg to about 32 mg/kg. pharmaceutical composition . A pharmaceutical composition for use according to any one of claims 1-4 , wherein said anti-Gal9 antibody is administered to said subject by intravenous injection at a dose of about 2 mg/kg to about 16 mg/kg. things . 2. The anti-Gal9 antibody is administered to the subject by intravenous injection at a dose of about 2 mg/kg, about 4 mg/kg, about 8 mg/kg, about 12 mg/kg, or about 16 mg/kg . A pharmaceutical composition for use according to any one of claims 1 to 5 . The pharmaceutical composition for use according to any one of claims 1 to 6, wherein said anti-Gal9 antibody is administered to the subject once every week. The pharmaceutical composition for use according to any one of claims 1-6, wherein said anti-Gal9 antibody is administered to the subject once every two weeks. The use is for 28 days wherein the anti-Gal9 antibody is administered to the subject on days 1 and 15 and the gemcitabine and /or paclitaxel is administered to the subject on days 1, 8 and 15 9. A pharmaceutical composition for use according to claim 8 , comprising a cycle. 10. A pharmaceutical composition for use according to claim 9 , wherein said paclitaxel is protein-bound paclitaxel, preferably nanoparticulate albumin-bound paclitaxel. 11. The pharmaceutical composition for use according to claim 9 or claim 10 , wherein said paclitaxel is administered to said subject intravenously at 125 mg/m ^<2> . A pharmaceutical composition for use according to any one of claims 1 to 11 , wherein said gemcitabine is administered to said subject at 1000 mg/m ² . The anti-galectin-9 antibody is shown as Light Chain Complementarity Determining Region 1 (CDR1) as SEQ ID NO: 1, Light Chain Complementarity Determining Region 2 (CDR2) as SEQ ID NO: 2, and SEQ ID NO: 3 light chain complementarity determining region 3 (CDR3) and/or heavy chain complementarity determining region 1 (CDR1) shown as SEQ ID NO: 4, heavy chain complementarity determining region 2 shown as SEQ ID NO: 5 (CDR2), and heavy chain complementarity determining region 3 ( CDR3 ) shown as SEQ ID NO:6. 14. Any of claims 1-13, wherein said anti-Gal9 antibody comprises a heavy chain variable region (V _H ) comprising the amino acid sequence of SEQ ID NO:7 and a light chain variable region (V _L ) comprising the amino acid sequence of SEQ ID NO:8. A pharmaceutical composition for use according to clause 1. A pharmaceutical composition for use according to any one of claims 1 to 14 , wherein said anti-Gal9 antibody is an IgG4 molecule. 16. The pharmaceutical composition for use according to claim 15, wherein said anti-Gal9 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:19 and a light chain comprising the amino acid sequence of SEQ ID NO: 15 . A pharmaceutical composition for use according to any one of claims 1 to 16 , wherein said subject is a human patient. The pharmaceutical composition for use according to any one of claims 1 to 17 , wherein said subject comprises galectin-9 positive cancer cells or immune cells. 19. The pharmaceutical composition for use according to claim 18 , wherein galectin-9 positive cancer cells or immune cells are detected within tumor organoids derived from said subject. the subject has elevated levels of galectin-9 compared to control values;
Optionally, the pharmaceutical composition for use according to any one of claims 1 to 19 , wherein said subject has elevated serum or plasma levels of galectin-9 compared to said control value. said subject had received at least one line of systemic anti-cancer therapy, or
said subject has no prior therapy with gemcitabine and/or paclitaxel, or has had prior therapy with gemcitabine and/or paclitaxel at least 6 months prior to administration of said anti-Gal9 antibody , a pharmaceutical composition for use according to any one of claims 1-20 . The subject has the following characteristics before, during, and/or after treatment:
(a) one or more tumor markers in a tumor biopsy sample from said subject, optionally wherein said one or more tumor markers are CA15-3, CA-125, CEA, CA19-9 and/or tumor markers, including alpha-fetoprotein;
( b) cytokine profile ; and (c) galectin 9 level. A pharmaceutical composition for use according to any one of claims 1 to 22 , wherein use further comprises monitoring the occurrence of one or more adverse effects in said subject. 24. The pharmaceutical composition for use according to claim 23 , wherein said one or more adverse effects comprise liver dysfunction, hematological toxicity, neurotoxicity, skin toxicity, gastrointestinal toxicity, or a combination thereof. Claim 23 or claim, wherein use further comprises reducing said dose of said anti-Gal9 antibody, said dose of said one or more chemotherapeutic agents, or both, if an adverse effect is observed. 24. A pharmaceutical composition for use according to 24 . administration of paclitaxel is discontinued if the subject has an aspartate transaminase (AST) level greater than 10 times the upper limit of normal (ULN), a bilirubin level greater than 5 times the ULN, or both; A pharmaceutical composition for use according to claim 25 . use further comprising reducing said dose of said anti-Gal9 antibody, said dose of said gemcitabine, said dose of said paclitaxel, or a combination thereof if moderate to severe liver dysfunction is observed; or ,
reducing the dose of said anti-Gal9 antibody, said gemcitabine, said paclitaxel, or combinations thereof, or any combination thereof, if severe hematologic, neurotoxicity, cutaneous, and/or gastrointestinal toxicity is observed after use; 27. A pharmaceutical composition for use according to claim 26 , further comprising the step of terminating administration. said dose of said paclitaxel is reduced from 100 mg/m ² to 75 mg/m ² and/or
28. A pharmaceutical composition for use according to claim 27 , wherein said dose of said gemcitabine is reduced to 800 mg/ ^m2 to 600 mg/ ^m2 .