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CN-122028934-A - Combination of CLDN18_2 antibody and chemotherapeutic drug and application thereof

CN122028934ACN 122028934 ACN122028934 ACN 122028934ACN-122028934-A

Abstract

Use of a Claudin 18.2 antibody in combination with a chemotherapeutic drug for the manufacture of a medicament for the treatment of a neoplastic disease, said combination optionally further comprising an immune checkpoint inhibitor.

Inventors

  • SUN JIYE

Assignees

  • 江苏奥赛康生物医药有限公司

Dates

Publication Date
20260512
Application Date
20241015
Priority Date
20231016

Claims (12)

  1. Use of a Claudin 18.2 antibody in combination with a chemotherapeutic drug for the preparation of a medicament for the treatment of a neoplastic disease; The Claudin 18.2 antibody has a heavy chain CDR1 shown in SEQ ID NO. 1, a heavy chain CDR2 shown in SEQ ID NO. 2, a heavy chain CDR3 shown in SEQ ID NO. 3, a light chain CDR1 shown in SEQ ID NO. 4, a light chain CDR2 shown in SEQ ID NO. 5 and a light chain CDR3 shown in SEQ ID NO. 6; The chemical treatment medicine is selected from one or more of pyrimidine analogue chemical treatment medicines, platinum chemical treatment medicines, taxol chemical treatment medicines and camptothecine chemical treatment medicines; the combination optionally further comprises an immune checkpoint inhibitor.
  2. A method of treating a neoplastic disease in a patient, characterized by administering to said patient a combination of a Claudin 18.2 antibody and a chemotherapeutic agent; The Claudin 18.2 antibody has a heavy chain CDR1 shown in SEQ ID NO. 1, a heavy chain CDR2 shown in SEQ ID NO. 2, a heavy chain CDR3 shown in SEQ ID NO. 3, a light chain CDR1 shown in SEQ ID NO. 4, a light chain CDR2 shown in SEQ ID NO. 5 and a light chain CDR3 shown in SEQ ID NO. 6; The chemical treatment medicine is selected from one or more of pyrimidine analogue chemical treatment medicines, platinum chemical treatment medicines, taxol chemical treatment medicines and camptothecine chemical treatment medicines; the combination optionally further comprises an immune checkpoint inhibitor.
  3. A pharmaceutical combination for the treatment of a neoplastic disease comprising a Claudin18.2 antibody and a chemotherapeutic agent; The Claudin 18.2 antibody has a heavy chain CDR1 shown in SEQ ID NO. 1, a heavy chain CDR2 shown in SEQ ID NO. 2, a heavy chain CDR3 shown in SEQ ID NO. 3, a light chain CDR1 shown in SEQ ID NO. 4, a light chain CDR2 shown in SEQ ID NO. 5 and a light chain CDR3 shown in SEQ ID NO. 6; The chemical treatment medicine is selected from one or more of pyrimidine analogue chemical treatment medicines, platinum chemical treatment medicines, taxol chemical treatment medicines and camptothecine chemical treatment medicines; the pharmaceutical combination optionally further comprises an immune checkpoint inhibitor.
  4. The use according to claim 1, or the method according to claim 2, or the pharmaceutical combination according to claim 3, wherein the Claudin 18.2 antibody has a heavy chain variable region as shown in SEQ ID No. 7 and a light chain variable region as shown in SEQ ID No. 8.
  5. The use according to claim 1, or the method according to claim 2, or the pharmaceutical combination according to claim 3, characterized in that the Claudin 18.2 antibody has a heavy chain as shown in SEQ ID No. 9 and a light chain as shown in SEQ ID No. 10.
  6. The use according to claim 1, or the method according to claim 2, or the pharmaceutical combination according to claim 3, The pyrimidine analog chemotherapeutic drug is selected from cytarabine, 5-fluorouracil, decitabine, gemcitabine, carmofur, capecitabine, doxifluridine, tegafur, or azacytidine; the platinum-based chemotherapeutic drug is selected from cisplatin, carboplatin, nedaplatin, oxaliplatin, or lobaplatin; The paclitaxel chemotherapeutic drug is selected from paclitaxel and docetaxel; The camptothecin chemotherapeutic drug is selected from camptothecine, hydroxycamptothecin, topotecan or irinotecan.
  7. The use of claim 1, or the method of claim 2, or the pharmaceutical combination of claim 3, wherein the immune checkpoint inhibitor is selected from one or more of an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-CTLA-4 antibody, a bi-targeting antibody comprising an anti-PD-1 antibody, a bi-targeting antibody comprising an anti-PD-L1 antibody, a bi-targeting antibody comprising an anti-CTLA-4 antibody.
  8. The use according to claim 1, or the method according to claim 2, or the pharmaceutical combination according to claim 3, wherein the immune checkpoint inhibitor is selected from the group consisting of nal Wu Liyou mab (Nivolumab), pamil mab (Pembrolizumab), terlipressin Li Shan mab (Toripalimab), singe Li Shan mab (Sintilimab), carlizumab (Camrelizumab), tirelimumab (Tislelizumab), pie An Puli mab (Penpulimab), sapalimumab (Zimberelimab), s Lu Lishan mab (Serplulimab), placimumab (Pucotenlimab), multi-tarolimumab (Dostarlimab), cimaprb Li Shan mab (Cemiplimab), palo Li Shan mab (Prolgolimab), divali You Shan mab (Durvalumab), atizumab (Atezolizumab), en Wo Lishan mab (Envafolimab), shu Geli mab (Sugemalimab), aldebelimumab (Adebrelimab), or avermectin (Avelumab).
  9. The use according to claim 1, or the method according to claim 2, or the pharmaceutical combination according to claim 3, characterized in that the neoplastic disease is selected from Claudin 18.2 positive cancers.
  10. The use according to claim 1, or the method according to claim 2, or the pharmaceutical combination according to claim 3, wherein the tumour disease is selected from gastric cancer, oesophageal cancer, or pancreatic cancer.
  11. The use according to claim 1, or the method according to claim 2, or the pharmaceutical combination according to claim 3, wherein the neoplastic disease is selected from Claudin 18.2 positive gastric cancer, esophageal cancer, or pancreatic cancer.
  12. The use according to claim 1, or the method according to claim 2, or the pharmaceutical combination according to claim 3, characterized in that the dose of Claudin 18.2 antibody is 6mg/kg, administered intravenously once every three weeks.

Description

Combination of CLDN18_2 antibody and chemotherapeutic drug and application thereof Technical Field The invention relates to application of a Claudin18.2 antibody and a chemotherapeutic drug combination in preparing a drug for treating tumor diseases. Background The stomach cancer is one of main malignant tumors threatening life health, the data show that 47.9 thousands of new cases of the stomach cancer in China and 37.4 thousands of death cases in 2020, and the relative survival rate of the stomach cancer in China is increased from 27.4% to 35.1% in 2003-2015. ("Chinese gastric cancer screening and early diagnosis and early treatment guide (2022)", chinese national center for cancer, http:// chinaccn. These statistics clearly indicate that gastric cancer limited treatment regimens are severely unsatisfactory for medical conditions. Antibodies are a relatively new class of targeted therapeutic drugs that have found wide application in the treatment of a variety of cancers. Antibody targeted therapies have the potential for higher specificity and lower side effects relative to many traditional non-antibody type tumor therapies. Claudin 18.2 has recently been found as a target for antibodies to treat gastric and esophageal cancers (J Hematol Oncol.2017 (1): 105). Meanwhile, the antibody is also a target point for developing antibody medicines for pancreatic cancer. There are a number of anti-Claudin 18.2 monoclonal antibodies currently in development, such as Zolbetuximab (IMAB 362), ASKB589, osemitamab (TST 001), etc. Cell tight junction proteins (claudins) are important molecules that constitute cell tight junctions, which determine the permeability of epithelial cells and also act to block the diffusion of cell membrane surface proteins and lipids. Claudin18 belongs to Claudins protein family and is encoded in humans by the Claudin18 gene. The human Claudin18 gene has two different exons No. 1, and after transcription, two protein subtypes Claudin18.1 and Claudin18.2, which have different sequences only at the N-terminus, are finally produced by alternative splicing. Claudin18.1 and Claudin18.2 are expressed with tissue specificity in humans, claudin18.1 is mainly expressed in lung tissue, and not in stomach tissue or gastric cancer. Claudin18.2 is expressed in normal tissues only on differentiated gastric mucosal epithelial cells as a highly specific cell surface molecule. Claudin18.2 molecules are expressed mostly in primary gastric cancer and its postmetastatic cancer types. Claudin18.2 is a very potential target for epithelial tumors due to its high specificity of normal tissue expression and its activated expression in a variety of cancers. Disclosure of Invention In a first aspect, the invention provides the use of a Claudin 18.2 antibody in combination with a chemotherapeutic agent in the manufacture of a medicament for the treatment of a neoplastic disease; The Claudin 18.2 antibody has a heavy chain CDR1 shown in SEQ ID NO. 1, a heavy chain CDR2 shown in SEQ ID NO. 2, a heavy chain CDR3 shown in SEQ ID NO. 3, a light chain CDR1 shown in SEQ ID NO. 4, a light chain CDR2 shown in SEQ ID NO. 5 and a light chain CDR3 shown in SEQ ID NO. 6; The chemical treatment medicine is selected from one or more of pyrimidine analogue chemical treatment medicines, platinum chemical treatment medicines, taxol chemical treatment medicines and camptothecine chemical treatment medicines; the combination optionally further comprises an immune checkpoint inhibitor. In a second aspect of the invention, there is provided a method of treating a neoplastic disease in a patient, characterized by administering to said patient a combination of a Claudin 18.2 antibody and a chemotherapeutic drug; The Claudin 18.2 antibody has a heavy chain CDR1 shown in SEQ ID NO. 1, a heavy chain CDR2 shown in SEQ ID NO. 2, a heavy chain CDR3 shown in SEQ ID NO. 3, a light chain CDR1 shown in SEQ ID NO. 4, a light chain CDR2 shown in SEQ ID NO. 5 and a light chain CDR3 shown in SEQ ID NO. 6; The chemical treatment medicine is selected from one or more of pyrimidine analogue chemical treatment medicines, platinum chemical treatment medicines, taxol chemical treatment medicines and camptothecine chemical treatment medicines; the combination optionally further comprises an immune checkpoint inhibitor. In a third aspect, the invention provides a pharmaceutical combination for the treatment of a neoplastic disease, comprising a Claudin 18.2 antibody and a chemotherapeutic agent; The Claudin 18.2 antibody has a heavy chain CDR1 shown in SEQ ID NO. 1, a heavy chain CDR2 shown in SEQ ID NO. 2, a heavy chain CDR3 shown in SEQ ID NO. 3, a light chain CDR1 shown in SEQ ID NO. 4, a light chain CDR2 shown in SEQ ID NO. 5 and a light chain CDR3 shown in SEQ ID NO. 6; The chemical treatment medicine is selected from one or more of pyrimidine analogue chemical treatment medicines, platinum chemical treatment medicines, taxol chemical treatment medicines and c