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Treatment of cancer

A cancer, colorectal cancer technology, applied in the direction of antibody medical ingredients, medical preparations containing active ingredients, drug combinations, etc.

Pending Publication Date: 2021-01-08
MEDIMMUNE LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Unfortunately, chemotherapeutics and / or targeted therapies do not provide adequate and / or durable antitumor responses in patients with non-MSI-H CRC

Method used

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  • Treatment of cancer
  • Treatment of cancer
  • Treatment of cancer

Examples

Experimental program
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example 1

[0243] Example 1: Dose Finding is a Phase 1 Multicenter Open-Label Single-Arm Dose-Escalation and Dose-Expansion Study of Durvalumab in Combination with Monarizumab

[0244] Conduct a phase 1 multicenter open-label single-arm dose-escalation and dose-expansion study of the combination of durvalumab and monalizumab (see WHO Drug Information [World Health Organization drug information] Volume 30, Number 1, 2016; Also known as IPH2201; an antibody having a heavy chain of SEQ ID NO: 11 and a light chain of SEQ ID NO: 15) to evaluate safety, tolerability, PK, immunogenicity, pharmacodynamics, and antitumor activity. The study consisted of 2 parts: dose escalation and dose expansion.

[0245] Subjects received durvalumab and monalizumab via 2 separate intravenous infusions. Subjects received durvalumab and monalizumab until unacceptable toxicity, documented confirmed progressive disease (PD), or subject withdrawal for another reason was documented.

[0246] Inclusion criteria inc...

example 2

[0259] Example 2: Responses in the CRC dose-expansion portion of a phase I clinical study in MSS colorectal cancer patients treated with monalizumab and durvalumab

[0260] The dose-expansion portion of the phase 1 study aims to enroll patients into four cohorts corresponding to cancers that are not adequately treated with existing therapies. One of these groups included subjects with recurrent or metastatic MSS-CRC. In the MSS-CRC group, all subjects were required to have documented mutation testing during screening and confirmation of tumor location from disease assessment for enrollment, and CRC cancers must be free of defective DNA mismatch repair (microsatellite instability ), as documented by passing tests.

[0261] Defective DNA mismatch repair is defined by any of the following: (il high-frequency microsatellite instability, where 2 or more microsatellite markers (BAT-25, BAT-26, NR-21, NR-24 , or MONO-27) group, or (ii) immunohistochemical analysis showed lack of pr...

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Abstract

The present invention relates to the use of NKG2A-neutralizing agents and PD-1 neutralizing agents to treat cancers, notably cancers that are not characterized by DNA mismatch repair deficiency. Provided are methods of treatment of a cancer, as well as compositions and kits useful for treating a cancer that is not characterized by DNA mismatch repair deficiency.

Description

technical field [0001] The present invention relates to the use of NKG2A neutralizers and PD-1 neutralizers for the treatment of cancer, in particular cancer not characterized by DNA mismatch repair deficiency. Includes treatment for MSS cancer. The present invention is particularly suitable for treating advanced recurrent or metastatic colorectal cancer. Background technique [0002] NK cell activity is regulated by complex mechanisms involving activating and inhibitory signals. Several different NK-specific receptors have been identified that play an important role in NK cell-mediated recognition and killing of HLA class I-deficient target cells. Natural cytotoxic receptors (NCRs) refer to a class of activated receptor proteins and the genes that express them, and these receptors are specifically expressed in NK cells. Examples of NCRs include NKp30, NKp44 and NKp46. These receptors are members of the Ig superfamily, and their cross-linking induced by specific monoclon...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K39/395A61P35/00
CPCA61K45/06C07K2317/21C07K16/2827A61K2039/507A61K2039/545C07K16/2803C07K2317/24A61K2300/00C07K16/2818A61P35/00C07K2317/76C07K2317/565
Inventor S·E·阿布杜拉A·K·古普塔宋绪阳
Owner MEDIMMUNE LTD