HER2 heterogeneity as a biomarker in cancer

Patent metadata

Field	Value
Publication number	US-12540359-B2
Application number	US-202017100357-A
Country	US
Kind code	B2
Filing date	Nov 20, 2020
Priority date	May 21, 2018
Publication date	Feb 3, 2026
Grant date	Feb 3, 2026

Abstract

A method for predicting responsiveness to a HER2-directed therapy by assessing HER2 heterogeneity in a tumor includes contacting a sample of the tumor with a biomarker-specific reagent that specifically binds to HER2 protein and detecting HER2 protein in the sample, contacting the sample of the tumor with a first nucleic acid probe that specifically binds HER2 genomic DNA and detecting HER2 gene amplification status in the sample, contacting the sample of the tumor with a second nucleic acid probe that specifically binds HER2 RNA and detecting HER2 RNA status in the sample scoring the HER2 protein (IHC), HER2 gene (DISH), and HER2 RNA (RNA-ISH), predicting that the tumor is responsive to the HER2-directed therapy if the tumor reveals a first foci having a first score and a second score, in which the first score and the second score are not the same.

First claim

The invention claimed is:

1 . A method for HER-2 directed therapy comprising
(a) assessing HER2 heterogeneity in a tumor, comprising
(i) contacting a sample of the tumor with a biomarker-specific reagent that specifically binds to HER2 protein and detecting HER2 protein in the sample,
(ii) contacting the sample of the tumor with a first nucleic acid probe that specifically binds HER2 genomic DNA, and detecting HER2 gene amplification status in the sample,
(iii) contacting the sample of the tumor with a second nucleic acid probe that specifically binds HER2 RNA, and detecting HER2 RNA status in the sample,
wherein the sample is a surgical tissue sample,
wherein the tumor is a solid tumor,
wherein the tumor is gastric cancer,

(b) scoring the HER2 protein (IHC), HER2 gene (DISH), and HER2 RNA (RNA-ISH),
wherein scoring is categorized as:
Group A for samples exhibiting IHC 3+ and DISH+, and RNA-ISH+,
Group B for samples exhibiting IHC 3+ and DISH−, and RNA-ISH−,
Group C for samples exhibiting IHC 2+ and DISH+, RNA-ISH+,
Group D for samples exhibiting IHC 2+ and DISH−, RNA-ISH−,
Group E for samples exhibiting IHC 1+ and DISH+, RNA-ISH+,
Group F for samples exhibiting IHC 1+ and DISH−, RNA-ISH−,
Group G for samples exhibiting IHC 0 and DISH+, RNA-ISH+, and
Group H for samples exhibiting IHC 0 and DISH−, RNA-ISH−,

(c) predicting that the tumor is responsive to the HER2-directed therapy if the tumor reveals a first foci having a first score selected from Group A to Group G and a second foci having a second score selected from Group A to Group G, wherein the first score and the second score are not the same, and (d) when the first score and the second score are indicative of a tumor being responsive to HER2-directed therapy, administering HER-2 directed therapy selected from the group consisting of trastuzumab, trastuzumab emtansine, pertuzumab, neratinib, and lapatinib.

2 . The method of claim 1 , wherein the contacting a sample of the tumor with a biomarker-specific reagent and the contacting the sample of the tumor with a first nucleic acid probe are both performed on a first section of the sample and the contacting the sample of the tumor with the second nucleic acid probe is performed on a second section of the sample, wherein the second section is a serial section of the first section.

3 . The method of claim 1 , wherein the contacting a sample of the tumor with a biomarker-specific reagent is performed on a first section of the sample, the contacting the sample of the tumor with the first nucleic acid probe is performed on a second section of the sample, and the contacting the sample of the tumor with the second nucleic acid probe is performed on a third section of the sample, wherein the first, the second, and the third sections are serial sections.

4 . The method of claim 1 , wherein the contacting a sample of the tumor with a biomarker-specific reagent and the contacting the sample of the tumor with a second nucleic acid probe are performed on a same section of the sample.

Assignees

• Genentech Inc
• Ventana Med Syst Inc
• Nat Cancer Ct

Inventors

• Murillo Adrian E
• Nitta Hiro
• Munroe Donald G
• Lo Amy A
• Kuwata Takeshi
• Kaito Akio
• Ochiai Atsushi

Classifications

• C12Q2600/118

  Prognosis of disease development · CPC title

• C12Q2561/113

  Real time assay · CPC title

• C12Q1/686

  Polymerase chain reaction [PCR] · CPC title

• C12Q1/682

  Signal amplification · CPC title

• C12Q1/6886 Primary

  for cancer (immunoassay for cancer G01N33/575) · CPC title