A5062532556- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Estrogen and related hormone effects
- Head and Neck Cancer Studies
- Radiomics and Machine Learning in Medical Imaging
- Computational Drug Discovery Methods
- Bladder and Urothelial Cancer Treatments
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Lung Cancer Diagnosis and Treatment
- Pancreatic and Hepatic Oncology Research
- HER2/EGFR in Cancer Research
- Ferroptosis and cancer prognosis
- Lung Cancer Research Studies
- RNA modifications and cancer
- Urinary and Genital Oncology Studies
- Esophageal Cancer Research and Treatment
- Colorectal Cancer Treatments and Studies
- Colorectal and Anal Carcinomas
- Virus-based gene therapy research
- Lymphoma Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Chemokine receptors and signaling
- Cancer, Hypoxia, and Metabolism
AstraZeneca (United Kingdom)
2016-2025
AstraZeneca (Brazil)
2005-2024
Cambridge Consultants (United Kingdom)
2023
Age UK
2022
GlaxoSmithKline (United Kingdom)
2022
AstraZeneca (United States)
2018-2020
Australian National University
2002
In the phase IV, open-label, single-arm study NCT01203917, first-line gefitinib 250 mg/d was effective and well tolerated in Caucasian patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (previously published). Here, we report EGFR mutation analyses of plasma-derived, circulating-free tumor DNA.
Purpose: Immunotherapies targeting programmed cell death-1 (PD-1) and death ligand-1 (PD-L1) demonstrate encouraging antitumor activity manageable tolerability in non-small lung cancer (NSCLC), especially patients with high tumor PD-L1 expression, as detected by companion or complementary diagnostic assays developed for individual agents. A laboratory is unlikely to use multiple assay platforms. Furthermore, commercially available are not standardized, different methods could lead...
A high-quality programmed cell-death ligand 1 (PD-L1) diagnostic assay may help predict which patients are more likely to respond anti-programmed cell death-1 (PD-1)/PD-L1 antibody-based cancer therapy. Here we describe a PD-L1 immunohistochemical (IHC) staining protocol developed by Ventana Medical Systems Inc. and key analytical parameters of its use in formalin-fixed, paraffin-embedded (FFPE) samples non-small lung (NSCLC) head neck squamous carcinoma (HNSCC). An anti-human rabbit...
Programmed cell death ligand-1 (PD-L1) expression levels in patient tumor samples have proven clinical utility across various cancer types. Several independently developed PD-L1 immunohistochemical (IHC) predictive assays are commercially available. Published studies using the VENTANA (SP263) Assay, (SP142) Dako IHC 22C3 pharmDx assay, 28-8 and laboratory-developed tests utilizing E1L3N antibody (Cell Signaling Technology), demonstrated differing of staining between assays, resulting...
NEPTUNE, a phase 3, open-label study, evaluated first-line durvalumab plus tremelimumab versus chemotherapy in metastatic NSCLC (mNSCLC).Eligible patients with EGFR and ALK wild-type mNSCLC were randomized (1:1) to (20 mg/kg every 4 weeks until progression) (1 for up four doses) or standard chemotherapy. Randomization was stratified by tumor programmed death-ligand 1 expression (≥25% <25%), histologic type, smoking history. The amended primary end point overall survival (OS) blood mutational...
Selumetinib (AZD6244, ARRY-142886)+docetaxel increases median overall survival (OS) and significantly improves progression-free (PFS) objective response rate (ORR) compared with docetaxel alone in patients KRAS mutant, stage IIIB/IV non-small-cell lung cancer (NSCLC; NCT00890825). Retrospective analysis of OS, PFS, ORR change tumour size at week 6 for different sub-populations codon mutations. In receiving selumetinib+docetaxel harbouring G12C or G12V mutations there were trends towards...
Abstract Purpose: Biomarkers that predict response to immune checkpoint inhibitors (ICI) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) are needed. This retrospective study assessed tumor mutational burden (TMB) outcomes the phase II HAWK CONDOR III EAGLE studies of durvalumab with without tremelimumab platinum-resistant R/M HNSCC. Patients Methods: Tumor samples from HAWK/CONDOR (N = 153) blood 247) were analyzed for TMB. Associations survival evaluated tissue...
Abstract Purpose: To determine the efficacy of AZD0530, an orally active small molecule Src inhibitor, in human pancreatic cancer xenografts and to seek biomarkers predictive activity. Experimental Design: Sixteen patient-derived from PancXenoBank collection at Johns Hopkins were treated with AZD0530 (50 mg/kg/day, p.o.) for 28 days. Baseline gene expression profiles differently expressed genes 16 tumors by Affymetrix U133 Plus 2.0 array used predict sensitivity independent group eight using...
Tumor programmed cell death ligand-1 (PD-L1) expression is a key biomarker to identify patients with non-small lung cancer who may have an enhanced response anti-programmed death-1 (PD-1)/PD-L1 treatment. Such treatments are used in conjunction PD-L1 diagnostic immunohistochemistry assays. We developed computer-aided automated image analysis customized scoring algorithm that was evaluated via correlation manual pathologist scores and determine comparability across The quantify the percentage...
Antibodies targeting the programmed cell death-1 (PD-1)/PD-ligand 1 (PD-1/PD-L1) checkpoint have shown promising clinical activity in patients with advanced urothelial carcinoma (UC). Expression of PD-L1 UC tumors has been investigated using different antibody clones, staining protocols, and scoring algorithms. The aim was to establish extent concordance among immunohistochemistry (IHC) assays.Tumor biopsy samples (N = 335) were assessed four commercially available assays: VENTANA SP263,...
Abstract Background Selective biomarkers may improve outcomes in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated immune checkpoint inhibitor therapy. We investigated three independent for association efficacy the randomized, phase III KESTREL study (NCT02551159) of first-line durvalumab monotherapy plus tremelimumab versus EXTREME regimen: programmed death ligand-1 (PD-L1) immunohistochemistry, blood tumor mutational burden (bTMB) via...
Abstract Purpose: Understanding the mutational landscape of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is important in identifying biomarkers to determine which patients may benefit from immune checkpoint inhibitors (ICIs). Patients Methods: The HAWK (NCT02207530), CONDOR (NCT02319044), EAGLE (NCT02369874) studies evaluated R/M HNSCC treatment with durvalumab or durvalumab-tremelimumab. Tumor tissue samples pooled HAWK/CONDOR (n=153) plasma cell-free DNA (n=285)...
The use of sensitive molecular techniques to detect rare cells in a population is increasing interest the pathologist, but detection limits often are poorly defined any given assay. We combined approaches real-time quantitative PCR with ARMS(TM) allele-specific amplification novel assay for detecting mutant K-ras sequences clinical samples.ARMS reactions were used seven commonly occurring mutations oncogene. These produce amino acid changes codon 12 (Gly Ala, Arg, Asp, Cys, Ser, or Val) and...
Several anti-programmed cell death-1 (PD-1) and death ligand-1 (PD-L1) therapies have shown encouraging safety clinical activity in a variety of tumor types. A potential role for PD-L1 testing identifying patients that are more likely to respond treatment is emerging. expression practice determined by one section per patient. Therefore, it critical understand the impact tissue sampling variability on patients’ classification. Resected non-small lung cancer (NSCLC), head neck squamous...
Context.— Clinical responses to anti–programmed death receptor-1 and ligand-1 (PD-L1) agents are generally improved in patients with high PD-L1 expression compared those low/negative across several tumor types, including urothelial carcinoma. Objective.— To validate a immunohistochemical diagnostic test carcinoma treated the anti–PD-L1 monoclonal antibody durvalumab. Design.— The Ventana (SP263) assay was validated for intended use formalin-fixed, paraffin-embedded samples studies addressing...
3025 Background: Determination of PD-L1 levels in tumors can help establish patient suitability for PD-1/PD-L1 targeted immunotherapies NSCLC. Biopsies may be taken from different sites (primary or metastatic) and also vary age, particularly if archived tissue is used. Understanding the impact sample types on expression will determine testing. Methods: FFPE samples 1546 patients screened ATLANTIC (NCT02087423) trial were successfully tested using Ventana IHC (SP263) test positivity cut off ≥...
6511 Background: In NSCLC, bTMB assessed from circulating tumor DNA shows promise as a predictive survival biomarker for immunotherapy, but its value in R/M HNSCC is uncertain. We evaluated predictor of HNSCC. Methods: EAGLE (NCT02369874) was randomized, open-label, phase 3 trial evaluating D (anti-PD-L1), or D+T (anti-CTLA-4), vs CT Patients (pts) with disease progression after platinum-based were randomized (1:1:1) to (10 mg/kg intravenous [IV] every 2 weeks [Q2W]), (20 IV Q4W) + T (1 Q4W...