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Methods of treating cancer with combination of platinum-based agent and anti-tissue factor antibody-drug conjugate

A technology of drug conjugates and antibodies, which can be used in drug combinations, anti-coagulation factor immunoglobulins, anti-tumor drugs, etc., and can solve problems such as inability to benefit

Pending Publication Date: 2022-06-21
展马博联合股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Most patients with second-line (and above) recurrent or metastatic cervical cancer do not benefit from pembrolizumab

Method used

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  • Methods of treating cancer with combination of platinum-based agent and anti-tissue factor antibody-drug conjugate
  • Methods of treating cancer with combination of platinum-based agent and anti-tissue factor antibody-drug conjugate
  • Methods of treating cancer with combination of platinum-based agent and anti-tissue factor antibody-drug conjugate

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0789] Texotuzumab vedotin is an antibody-drug conjugate comprising an antibody that binds tissue factor (TF), a protease cleavable linker, and the microtubule disrupting agent MMAE. TF is a protein that is aberrantly expressed in a variety of tumors, including cervical cancer, and is associated with poor prognosis. see Y et al Clin Chim Acta.364(1-2):12-21,2006 and Cocco E et al BMC Cancer.11:263,2011. Texotuzumab vedotin selectively targets TF to deliver a clinically validated toxic payload to tumor cells. See Breij EC et al Cancer Res. 2014;74(4):1214-1226 and Chu AJ. IntJ Inflam. 2011;2011. doi: 10.4061 / 2011 / 367284.

[0790] Cisplatin (a platinum-based agent) is used in combination with paclitaxel (a microtubule inhibitor) as a standard-of-care option for the treatment of stage IVB, recurrent, or persistent cervical cancer. See Kitagawa R et al., J Clin Oncol., 33:2129-2135, 2015. This article evaluates texotuzumab vedotin in combination with a platinum-based agent su...

Embodiment 2

[0800] This article evaluates texotuzumab vedotin in combination with a platinum-based agent such as cisplatin for the treatment of bladder cancer.

[0801] Materials and methods

[0802] In female Crl::NMRI-Foxn1 nu (Envigo RMS SAR, France) The in vivo antitumor efficacy of texotuzumab vedotin in combination with cisplatin was evaluated in the PDX mouse model of nude mice (Charles River Discovery Research Services). Xenografts are derived from tumor samples from cancer patients. After initial implantation into nude mice, PDX models were established and characterized. Tumor xenografts were passaged approximately 3-5 times until a stable growth pattern was established. Tumor fragments were obtained from serially passaged xenografts in nude mice. Tumors were cut into 3-4 mm diameter pieces and placed in phosphate buffered saline (PBS) until implanted subcutaneously. The experiment used a bladder cancer PDX model (bladder cancer xenograft model BXF1036; Charles River Disco...

Embodiment 3

[0810] This article evaluates texotuzumab vedotin in combination with a platinum-based agent such as carboplatin for the treatment of cervical cancer.

[0811] Materials and methods

[0812] Evaluation of the texotuzumab vedotin combination in a patient-derived xenograft (PDX) mouse model in female BALB / c nude mice (Crown Bioscience [Taicang] Inc.) In vivo antitumor efficacy of cisplatin. Xenografts are derived from tumor samples from cancer patients. Tumor fragments were obtained from serially passaged xenografts in nude mice. Tumors were cut into 2-4 mm diameter pieces and placed in phosphate buffered saline (PBS) until implanted subcutaneously. The experiment used cervical cancer PDX model ( Cervical xenograft model CV1248[P3]; Crown Biotech Ltd). Determine tumor size by caliper measurements at least twice a week and calculate tumor volume as 0.5 x length x width 2 . When the tumor reaches 150mm 3 The mice were randomly divided into 7 groups (10 mice in each trea...

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Abstract

The present invention provides combinations of a platinum-based agent (e.g., carboplatin) and an antibody-drug conjugate that binds to tissue factor (TF) (e.g., tesosoil monoclonal antibody vidottine) and their use in methods of treating cancer, such as bladder cancer and cervical cancer. The present invention also provides compositions and kits comprising a platinum-based agent (e.g., carboplatin) and a TF-binding antibody-drug conjugate (e.g., tesosoil monoclonal antibody vidottine) for use in the treatment of cancer, such as bladder cancer and cervical cancer.

Description

technical field [0001] The present invention relates to methods of treating cancer, such as bladder cancer and cervical cancer, with combinations of platinum-based agents and anti-tissue factor (anti-TF) antibody-drug conjugates. [0002] Sequence Listing Submitted as ASCII Text File [0003] The following submission as an ASCII text file is hereby incorporated by reference in its entirety: Computer Readable Format (CRF) Sequence Listing (File Name: 761682002840SEQLIST.TXT, Date of Record: October 22, 2020, Size: 6KB). Background technique [0004] Tissue factor (TF), also known as thromboplastin, factor III, or CD142, is a protein present in the subendothelial tissue, platelets, and white blood cells that is required for the formation of thrombin starting from the zymogen prothrombin. The formation of thrombin ultimately leads to blood clotting. TF enables cells to initiate the coagulation cascade, and it acts as a high affinity receptor for coagulation factor Vila (FVIIa...

Claims

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Application Information

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IPC IPC(8): A61K47/68A61K31/555A61P35/00
CPCA61K47/6849A61P35/00A61K31/555A61K33/243A61K47/68031A61K2300/00A61K47/65A61K38/05C07K16/36A61K47/6803
Inventor R·A·兰格瓦拉E·C·W·布里吉S·维普罗根O·O·阿比多也L·V·妮卡西欧
Owner 展马博联合股份有限公司