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Therapeutic and diagnostic methods for cancer

A kind of therapy, cancer technology, applied in chemical instruments and methods, medical automated diagnosis, biochemical equipment and methods, etc., can solve problems such as inappropriate health conditions

Pending Publication Date: 2020-08-04
GENENTECH INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, some patients are unsuitable or unwilling to undergo biopsy to obtain tumor samples for somatic mutation analysis, for example due to their health status
[0005] Therefore, there is an unmet need for an orthogonal, non-invasive diagnostic method that enables the analysis of TMB in patient samples without the need for tumor tissue biopsies

Method used

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  • Therapeutic and diagnostic methods for cancer
  • Therapeutic and diagnostic methods for cancer
  • Therapeutic and diagnostic methods for cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0569] Embodiment 1. Method

[0570] A blood-based assay was used to assess the association between clinical response to treatment with atezolizumab (MPDL3280A) and hematological tumor mutational burden (bTMB) score in patients with non-small cell lung cancer (NSCLC) who Two clinical trials, Phase II clinical trial POPLAR (Clinical Trial ID No: NCT01903993) and Phase III clinical trial OAK (Clinical Trial ID No: NCT02008227), in which atezolizumab was administered as monotherapy, were enrolled.

[0571] Research design

[0572] Pre-treatment blood samples from patients with NSCLC enrolled in the POPLAR and / or OAK studies in which atezolizumab was administered as monotherapy were assessed for bTMB score and / or maximum somatic allele frequency (MSAF).

[0573] The POPLAR (Clinical Trial ID: NCT01903993) patient population evaluated for the bTMB score consisted of 273 patients. Patients are eligible for inclusion in the POPLAR study if they have: locally advanced or metastatic ...

Embodiment 2

[0631] Example 2. Analysis of the Association Between bTMB Score and Clinical Response to Atezolizumab Treatment in Patients with NSCLC

[0632]To assess whether the bTMB score could be used as a predictive biomarker of patient response to atezolizumab treatment, bTMB score was assessed in pre-treatment blood samples obtained from patients in the POPLAR or OAK trials as described in Example 1. Overall survival (OS) and progression-free survival from the POPLAR and OAK trials were observed in patients with a positive diagnosis (Dx+) based on a bTMB score equal to or higher than the reference score of ≥4 to ≥20 and ≥4 to ≥26, respectively Period (PFS) ( Figure 1A , Figure 1B , Figure 2A with Figure 2B ). In POPLAR, PFS and OS benefits were observed at all bTMB score cutoffs between ≥10 and ≥20 (eg, between ≥12 and ≥20) ( Figure 1A with Figure 1B ). In both the POPLAR and OAK studies, Dx+ patients with a bTMB score greater than or equal to a reference bTMB score of 18 ...

Embodiment 3

[0653] Example 3: bTMB is independent of PD-L1 IHC and histology

[0654] Tables 10 and 11 show the clinical characteristics of the bTMB subgroup in OAK. Within OAK BEP, positive bTMB status (≥16) was associated with smoking (P=1.3e-10), which was associated with substantial mutagen exposure, SLD of target lesions at baseline (P=4.8e-08), metastatic sites The number (P=0.0055) is consistent with the expression of PD-L1 (TC1 / 2 / 3 or IC1 / 2 / 3 (P=0.0062)) (Table 10). Baseline characteristics were balanced between treatment groups above a bTMB cutpoint of > 16 (Table 11). Mean bTMB values ​​were 11.22 (95% CI: 10.09, 12.36) in patients with non-squamous histology and 12.4 (95% CI: 11, 13.8) in those with squamous histology ( Figure 10 ).

[0655] Table 10. Characteristics of the subgroup with bTMB ≥ 16 in the OAK study

[0656]

[0657]

[0658] TC0 and IC0, <1% of TC and IC express PD-L1; TC1 / 2 / 3 or IC1 / 2 / 3, ≥1% of TC or IC express PD-L1; TC2 / 3 or IC2 / 3, ≥5 % of TC or IC ...

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Abstract

The present invention provides therapeutic, diagnostic, and prognostic methods for cancer. The invention provides methods of treating a cancer, methods of determining whether an individual having a cancer is likely to respond to a treatment including an immune checkpoint inhibitor (e.g., a PD-L1 axis binding antagonist), methods of predicting responsiveness of an individual having a cancer to a treatment including an immune checkpoint inhibitor (e.g., a PD-L1 axis binding antagonist), methods of selecting a therapy for an individual having a cancer, methods of providing a prognosis for an individual having a cancer, and methods of monitoring a response of an individual having a cancer, based on a blood tumor mutational burden (bTMB) score or a maximum somatic allele frequency (MSAF) from asample (e.g., a whole blood sample, a plasma sample, a serum sample, or a combination thereof) from the individual.

Description

[0001] field of invention [0002] Provided herein are diagnostic, therapeutic and prognostic methods for treating cancer using immune checkpoint inhibitors (eg, PD-L1 axis binding antagonists). In particular, the present invention provides methods for patient selection and diagnosis, methods of treatment, and diagnostic kits. Background technique [0003] Cancer remains one of the deadliest threats to human health. In the United States, cancer affects nearly 1.3 million new patients each year and is the second leading cause of death after heart disease, accounting for about a quarter of all deaths. It is also predicted that cancer may overtake cardiovascular disease within 5 years and become the number one cause of death. Solid tumors are responsible for the majority of these deaths. Although remarkable advances have been made in the medical treatment of some cancers, the overall 5-year survival rate for all cancers has improved by only about 10% over the past 20 years. S...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/574G16H50/20G16B30/00A61K45/00A61K39/395A61P35/00A61P35/02
CPCC07K16/2827C12Q1/68C12Q1/6883G01N33/57492A61K2039/505A61K2039/55C07K2317/24C12Q2600/156G01N2333/70532G01N2800/52A61P35/00Y02A90/10G01N33/574G16H50/30C07K16/2896G16H50/50G06F16/285G16H50/70C07K14/70535G16H50/20
Inventor C·A·卡明斯李艳S·M·保罗E·B·施莱夫曼D·夏姆斯D·法布里齐奥D·利伯G·A·奥特M·肯尼迪T·克拉克D·利普森何洁钟山
Owner GENENTECH INC
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