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Anti igf, anti pd-1 Anti-cancer combination therapy

A composition and antibody technology, applied in the direction of drug combination, antibody medical components, chemical instruments and methods, etc.

Inactive Publication Date: 2020-05-12
BOEHRINGER INGELHEIM INT GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Despite compelling preclinical rationale, results from trials of IGF-1R inhibitors in combination with chemotherapy or other targeted therapies have shown limited clinical benefit (Langer et al., J Clin Oncol. 2014;32(19) :2059-66; Fuchs et al., Ann Oncol. 2015; 26(5):921-7, Sclafani et al., J Natl Cancer Inst. 2015; 107(12):djv258; Van Cutsem et al., Clin Cancer Res. 2014;20(16):4240-50)

Method used

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  • Anti igf, anti pd-1 Anti-cancer combination therapy
  • Anti igf, anti pd-1 Anti-cancer combination therapy
  • Anti igf, anti pd-1 Anti-cancer combination therapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0200] In Vivo Antitumor Efficacy of the Combination of Compound A and Compound B in a Colon Cancer Model

[0201] Materials and methods

[0202] The antitumor efficacy of the combination of Compound A and Compound B was investigated in a syngeneic mouse tumor model derived from the murine colon carcinoma cell line MC-38. Tumor cells were implanted subcutaneously into immunocompetent syngeneic C57Bl / 6 6- to 8-week-old female mice (in 30 μl Matrigel, 1 x 10 6 tumor cells) and established tumors three days before starting treatment. Compound B (PD-1 mouse antibody, 10 mg / Kg, once every three or four days), compound B (PD-1 mouse antibody, 10 mg / Kg, every three or four days) were administered intraperitoneally (ip) to mice. once a day) and compound A (BI-IGF, 200mg / Kg, once every seven days) or IgG isotype control antibody (10mg / Kg, once every three or four days) for 15-32 days. Tumor volumes were measured three times a week using calipers. Calculate the volume of each tumor ...

Embodiment 2

[0210] In Vivo Antitumor Efficacy of the Combination of Compound A and Compound B in a Breast Cancer Model

[0211] Materials and methods

[0212] The antitumor efficacy of the combination of Compound A and Compound B was investigated in a syngeneic mouse tumor model derived from the breast cancer cell line EMT-6. Tumor cells were implanted subcutaneously into immunocompetent syngeneic BALB / c 6- to 8-week-old female mice (in 30 μl Matrigel, 1 x 10 6 tumor cells) and establish tumors 6 to 10 days before starting treatment. Compound B (PD-1 mouse antibody, 10 mg / Kg, once every three or four days), compound B (PD-1 mouse antibody, 10 mg / Kg, every three or four days) were administered intraperitoneally (ip) to mice. once a day) and compound A (BI-IGF, 200mg / Kg, once every seven days) or IgG isotype control antibody (10mg / Kg, once every three or four days) for 10-35 days. Tumor volumes were measured three times a week using calipers. Calculate the volume of each tumor [mm] acco...

Embodiment 3

[0215] Effects of Compound A and Compound B Combination on Intratumoral Regulatory T Cells (Tregs) in a Colon Cancer Model

[0216] Materials and methods

[0217] In a syngeneic mouse tumor model derived from the colon cancer cell line MC-38, the reduction of intratumoral Treg following combined treatment with compound A and compound B was investigated. Tumor cells were implanted subcutaneously into immunocompetent syngeneic C57Bl / 6 6- to 8-week-old female mice (in 30 μl Matrigel, 1 x 10 6 tumor cells) and establish tumors 3 to 6 days before starting treatment. Intraperitoneal (ip) administration of compound A (BI-IGF, 200mg / Kg, once every seven days), compound B (mouse antibody to PD-1, 10mg / Kg, once every three or four days), compound Combination of B (PD-1, 10mg / Kg, once every three or four days) and compound A (BI-IGF, 200mg / Kg, once every seven days), or IgG isotype control antibody (10mg / Kg, every once every three or four days) for 10-35 days. Tumor volumes were meas...

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Abstract

The disclosure relates to the combined use of certain anti-IGF antibody molecules with PDl antagonists for the treatment of cancer. It further relates to pharmaceutical compositions and kits comprising such anti-IGF antibody molecules and antagonists.

Description

technical field [0001] The present invention relates to combination therapy for the treatment of cancer and compounds useful in such combination therapy. The compounds used in combination are insulin-like growth factor (IGF) antagonists and PD-1 antagonists. Background technique [0002] There is a large scientific, epidemiological, and clinical literature concerning the role of IGF in the initiation, progression, and metastasis of many different cancer types (by Jerome et al., End. Rel. Cancer 10:561-578, 2003; and Pollak et al. People, Nature Rev. Can. 4:505-518, reviewed in 2004). [0003] Various strategies are being used to inhibit the IGF pathway, such as anti-receptor monoclonal antibodies (including ganitumab, cixutumumab, and dalotuzumab), tyrosine Kinase inhibitors (TKIs, including dual IGF-IR and InsR tyrosine kinase inhibitors BMS-754807, KW2450 and linsitinib) and anti-IGF ligand antibodies (dusigitumab=MEDI-573, Astra Zeneca / Med Immune). These drugs have bee...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K38/17C07K16/22C07K16/28
CPCA61K39/39558C07K16/22C07K16/2818C07K16/2827C07K2317/565C07K2317/76A61P35/00A61K2039/507
Inventor U·魏尔·切尔尼洛夫斯基M·雷斯克
Owner BOEHRINGER INGELHEIM INT GMBH
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