Tumor mutation burden alone or in combination with immune markers as biomarkers for predicting response to targeted therapy

A targeted therapy and targeted technology, applied in the field of biomarkers, can solve problems such as insufficient cure

Pending Publication Date: 2021-05-28
NOVARTIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Finding the right therapy for cancer patients with melanoma (stages I-IV) is critical because cancer can grow and metastasize extremely rapidly and due to the presence of undetected disseminated tumor cells, surgical resection alone may not enough to heal

Method used

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  • Tumor mutation burden alone or in combination with immune markers as biomarkers for predicting response to targeted therapy
  • Tumor mutation burden alone or in combination with immune markers as biomarkers for predicting response to targeted therapy
  • Tumor mutation burden alone or in combination with immune markers as biomarkers for predicting response to targeted therapy

Examples

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example 1

[0246] Updated recurrence-free survival (RFS) and Biomarker Analysis

[0247] Background: A preliminary analysis of COMBI-AD (NCT 01682083) showed a significant improvement in RFS with adjuvant D+T relative to placebo (Pbo; HR, 0.47; P<.001). We provide RFS analysis with extended follow-up (FU), cure rate models, and biomarker analysis.

[0248] Methods: COMBI-AD was a randomized phase 3 trial evaluating 12 months of adjuvant D+T versus Pbo in patients with resected BRAF V600-mutant stage III melanoma. A Weibull mixed cure rate model was used to estimate the proportion of patients who would not relapse. In baseline tissue samples by sequencing 570 genes and using The platform performs gene expression profiling (GEP) to examine mutation profiles and gene expression signatures (GES).

[0249] Results: Median FU was 44 months (D+T) and 42 months (Pbo); 177 / 438 patients (41%) in the D+T group and 254 / 432 patients (59%) in the Pbo group %) have relapsed / died. Median RFS (NR;...

example 2

[0252] Genomic profile, tumor mutation burden (TMB), immune gene expression signature, and clinical outcome after adjuvant dabrafenib / trametinib or placebo in stage 3 melanoma: relevance of the phase III COMBI-AD trial analyze

[0253] method

[0254] Tissue samples and DNA / RNA extraction

[0255] All patients in the Combi-AD trial underwent surgical resection of the primary skin tumor and lymph nodes. Submit tissue samples for central BRAF testing at Screening. With patient consent, remaining tissue material was used for exploratory biomarker studies. Sections of 5 (±1) μm thickness were cut from all blocks received. Pathologists visually inspected archived FFPE slides and freshly dissected slides from tumor blocks to identify and annotate the approximate percentage of tumor content and total tumor area (mm2) in the region of interest (ROI) . Depending on tumor cell content, 4-12 slides were macroscopically dissected and used for DNA / RNA isolation. Further processing w...

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Abstract

The invention relates to the use of biomarkers for predicting the response to cancer (e.g. melanoma) treatments, for selecting a treatment for a cancer patient (e.g. using targeted therapy, e.g. using a BRAF and / or MEK inhibitor), for stratifying cancer patients into different treatment groups, for treating cancer patients, and for predicting clinical outcome in cancer.

Description

technical field [0001] The present invention relates to biomarkers for predicting response to treatment of cancer (e.g. melanoma), for selecting treatment for cancer patients (e.g. using targeted therapy, e.g. using BRAF and / or MEK inhibitors), for targeting cancer Uses for stratification of patients into different treatment groups, for treating cancer patients, and for predicting clinical outcome of cancer. Background technique [0002] Cancer is the leading cause of death worldwide, killing more than 8 million people every year. Melanoma is a malignant tumor resulting from the uncontrolled proliferation of pigment-producing cells. Melanoma is one of the most common cancers, its prevalence is increasing, and it accounts for the majority of skin cancer deaths. [0003] In addition to traditional cancer therapies such as chemotherapy and radiation, new strategies have been developed to treat cancer. These include targeted therapies and immuno-oncology therapies. Targeted ...

Claims

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Application Information

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Patent Type & AuthorityApplications(China)
IPC IPC(8): C12Q1/6886
CPCC12Q1/6886C12Q2600/158C12Q2600/106C12Q2600/156
InventorJ·C·布拉泽J·加勒特C·坎贝尔
OwnerNOVARTIS AG