Diagnostic and therapeutic methods for cancer

A kind of therapy and cancer technology, applied in the field of cancer diagnosis and treatment, can solve the problems of timely detection and treatment, downregulation of T cell activation, suppression of anti-tumor immune activity, etc.

Pending Publication Date: 2019-12-27
F HOFFMANN LA ROCHE & CO AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Formation of PD-L1 / PD-1 and PD-L1 / B7-1 complexes negatively regulates T cell receptor signaling, leading to subsequent downregulation of T cell activation and suppression of antitumor immune activity
[0008] Although there have been significant advances in the medical treatment of certain cancers, the overall 5-year survival rate for all cancers has only improved by about 10% over the past 20 years
In particular, malignant solid tumors metastasize and grow rapidly in an uncontrolled manner, making their timely detection and treatment extremely difficult

Method used

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  • Diagnostic and therapeutic methods for cancer
  • Diagnostic and therapeutic methods for cancer
  • Diagnostic and therapeutic methods for cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0815] Example 1: Immune Score Expression Levels of (i) PD-L1, CXCL9, and IFNG or (ii) PD-L1, IFNG, GZMB, and CD8A in Patients with Non-Small Cell Lung Cancer (NSCLC) Association between clinical responses to zizumab (MPDL3280A) treatment

[0816] An RNA-based molecular assay was used to assess response to the anti-PD-L1 antibody atezolizumab in patients with non-small cell lung cancer (NSCLC) enrolled in a phase III clinical trial in which atezolizumab was administered as monotherapy (MPDL3280A) Association between clinical response to treatment and immune score expression levels of (i) PD-L1, CXCL9, and IFNG or (ii) PD-L1, IFNG, GZMB, and CD8A.

[0817] Research design

[0818] The OAK (Clinical Trial ID No.: NCT02008227) patient population consisted of 753 patients to evaluate the expression levels of (i) PD-L1, CXCL9, and IFNG and (ii) PD-L1, IFNG, GZMB, and CD8A. If the patient has locally advanced or metastatic (e.g., stage IIIB, stage IV, or recurrent) NSCLC; during o...

Embodiment 2

[0841] Example 2: Association Between Expression Levels of PD-L1, CXCL9, and IFNG and Clinical Response to Treatment with Atezolizumab (MPDL3280A) in Patients with NSCLC

[0842] An RNA-based molecular assay was used to assess the clinical response to treatment with the anti-PD-L1 antibody atezolizumab (MPDL3280A) in individuals with NSCLC enrolled in a phase II clinical trial in which atezolizumab was administered as monotherapy Correlation between response and expression levels of PD-L1, CXCL9, and IFNG.

[0843] Research design

[0844] The POPLAR (Clinical Trial ID No.: NCT01903993) patient population evaluating PD-L1, CXCL9, and IFNG expression levels consisted of 215 patients. If the patient has locally advanced or metastatic (e.g., stage IIIB, stage IV, or recurrent) NSCLC; during or after treatment with a prior platinum-containing regimen for locally advanced, unresectable / inoperable, or metastatic NSCLC Disease progression, or disease recurrence within 6 months of t...

Embodiment 3

[0855] Example 3: Association Between Expression Levels of PD-L1, CXCL9, and IFNG and Clinical Response to Treatment with Atezolizumab (MPDL3280A) in Patients with UBC

[0856] Use of an RNA-based molecular assay to assess response to atezolizumab in individuals with advanced urothelial bladder cancer (UBC) enrolled in a phase II clinical trial (IMvigor210 trial) in which atezolizumab was administered as monotherapy (MPDL3280A), Association between clinical response to anti-PD-L1 antibody therapy and expression levels of PD-L1, CXCL9, and IFNG.

[0857] Research design

[0858] The expression levels of PD-L1, CXCL9, and IFNG were assessed on pre-treatment tumor specimens from patients with advanced UBC in cohort 2 of the phase II IMvigor210 trial (Clinical Trial ID No.: NCT02108652). If patient has histologically or cytologically proven locally advanced or metastatic transitional cell carcinoma or urothelium (eg, renal pelvis, ureter, bladder, or urethra); disease progression...

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Abstract

The present invention provides diagnostic methods, therapeutic methods, and compositions for the treatment of cancer. The invention is based, at least in part, on the discovery that an immune-score expression level based on one or more of PD-L1, CXCL9, IFNG, GZMB, CD8A, and PD-1 in a sample obtained from an individual having cancer can be used in methods of predicting the therapeutic efficacy of treatment with a PD-L1 axis binding antagonist (e.g., a PD-L1 binding antagonist (e.g., anti-PD-L1 antibody, e.g., atezolizumab (MPDL3280A)) or a PD-1 binding antagonist (e.g., anti-PD-1 antibody)).

Description

[0001] sequence listing [0002] This application, containing a Sequence Listing, has been filed electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on March 30, 2018, is named 50474-158WO3_Sequence_Listing_3.30.18_ST25 and is 96,571 bytes in size. [0003] field of invention [0004] The present invention is directed to diagnostic and therapeutic methods for the treatment of cancer using PD-L1 axis binding antagonists. Also provided are related assays and kits. [0005] Background of the invention [0006] Cancer remains one of the deadliest threats to human health. Cancer strikes nearly 1.3 million new patients each year in the United States and is the second leading cause of death after heart disease, accounting for about 1 in 4 deaths. It is also predicted that cancer may overtake cardiovascular disease as the number one cause of death within five years. Solid tumors are responsible for most of those deaths. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886
CPCC12Q1/6886C12Q2600/106C12Q2600/158A61P35/00A61K31/337A61K31/555A61K38/00C07K16/22C07K16/2827C07K2317/76G01N33/5011G01N2333/57G01N2333/70517G01N2333/70532G01N2333/7158G01N2333/96436G01N2800/52G01N2800/7028
Inventor M·科瓦内茨M·侯赛尼W·邹
Owner F HOFFMANN LA ROCHE & CO AG
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