A5006249212- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Head and Neck Cancer Studies
- Cancer Genomics and Diagnostics
- Radiomics and Machine Learning in Medical Imaging
- Bladder and Urothelial Cancer Treatments
- Urinary and Genital Oncology Studies
- Colorectal and Anal Carcinomas
- Endometrial and Cervical Cancer Treatments
- Ferroptosis and cancer prognosis
- Esophageal Cancer Research and Treatment
- Lymphoma Diagnosis and Treatment
- Cervical Cancer and HPV Research
- Cancer, Stress, Anesthesia, and Immune Response
- Peptidase Inhibition and Analysis
- Lung Cancer Research Studies
- Glioma Diagnosis and Treatment
- Reproductive System and Pregnancy
- Cancer Diagnosis and Treatment
AstraZeneca (United Kingdom)
2017-2025
Cambridge Consultants (United Kingdom)
2023
Targeting the programmed cell death protein 1 (PD-1)/programmed ligand (PD-L1) axis has demonstrated clinical benefit in recurrent/metastatic head and neck squamous carcinoma (R/M HNSCC). Combining immunotherapies targeting PD-L1 cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) shown evidence of additive activity several tumor types. This phase III study evaluated efficacy durvalumab (an anti-PD-L1 monoclonal antibody) or plus tremelimumab anti-CTLA-4 versus standard care (SoC) R/M HNSCC...
<h3>Importance</h3> Dual blockade of programmed death ligand 1 (PD-L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) may overcome immune checkpoint inhibition. It is unknown whether dual can potentiate antitumor activity without compromising safety in patients with recurrent or metastatic head neck squamous cell carcinoma (R/M HNSCC) low no PD-L1 tumor expression. <h3>Objective</h3> To assess objective response rate durvalumab combined tremelimumab. <h3>Design, Setting,...
Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis. The phase III KESTREL study evaluated the efficacy of durvalumab [programmed death-ligand 1 (PD-L1) antibody] without tremelimumab [cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody], versus EXTREME regimen in patients R/M HNSCC.
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 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...
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...
<h3>Objectives</h3> In locally-advanced cervical cancer (LACC), platinum-based chemoradiotherapy (CRT) has been the standard- of-care treatment for >20 years. CALLA is first global Phase 3 study evaluating immune checkpoint inhibition (durvalumab) versus placebo in combination with and following CRT LACC (NCT03830866). <h3>Methods</h3> Newly-diagnosed, untreated patients (FIGO 2009 stages IB2-IIB node positive, IIIA-IVA any status) were randomized 1:1 to durvalumab (1500 mg IV) or Q4W, a...
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)...
<p>Supplementary Figure S1. Somatic SNVs/indels derived from tumor tissue and plasma samples in patients with OPC. counts detected the HAWK/CONDOR EAGLE by HPV status according to smoking history.</p>
<p>Supplementary Figure S4. TERT mutations and response to immunotherapy SoC chemotherapy in the EAGLE study. Kaplan-Meier plots of OS PFS for patients treated with durvalumab plus tremelimumab (A B), (C D), (E F) study.</p>
<p>Supplementary Figure S3. TP53 mutations and resistance to immunotherapy SoC chemotherapy in R/M HNSCC assessed by PFS. Kaplan-Meier plot of PFS the wild type mutant subgroups for patients treated with ICI HAWK/CONDOR study (A), EAGLE (B), or (C). Somatic mutation counts status detected plasma samples (D).</p>
<p>Supplementary Figure S2. Scatterplot with Spearman’s rho correlation of 47 genes (tissue prevalence >3% and plasma >5%) between HAWK/CONDOR tissue EAGLE data.</p>
<div>AbstractPurpose:<p>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 (ICI).</p>Experimental Design:<p>The HAWK (NCT02207530), CONDOR (NCT02319044), EAGLE (NCT02369874) studies evaluated R/M HNSCC treatment with durvalumab or durvalumab–tremelimumab. Tumor tissue samples pooled HAWK/CONDOR...
<p>Supplementary Figure S5. CCND1 and PIK3CA/PIK3CB amplification response to immunotherapy SoC chemotherapy in the EAGLE study. Kaplan-Meier plot of OS wild-type subgroups for patients treated with durvalumab plus tremelimumab (A), (B), or (C) (D), (E), (F) study.</p>
Programmed cell death ligand-1 (PD-L1), expressed on both tumor cells (TC) and tumor-associated immune (IC), has been shown to be a useful biomarker predictive of response anti-PD-L1 agents in certain types. In recurrent or metastatic head neck squamous carcinoma (R/M HNSCC), there is growing interest the role PD-L1 expression ICs, as well TCs, for predicting checkpoint inhibitors. Using pooled data from phase II HAWK CONDOR studies, we investigated association baseline with durvalumab...
Abstract Background Programmed cell death ligand-1 (PD-L1) expression on tumor cells (TCs) is associated with improved survival in patients head and neck squamous carcinoma (HNSCC) treated immunotherapy, although its role as a prognostic factor controversial. This study investigates whether tumoral of PD-L1 marker recurrent and/or metastatic (R/M) HNSCC standard chemotherapy. Methods retrospective, multicenter, noninterventional assessed archival R/M tissue samples using the VENTANA (SP263)...
6548 Background: Baseline tumor and germline biomarkers in R/M HNSCC were analyzed for predictive potential pts benefitting from D or D+T. Methods: In HAWK (NCT02207530), 112 (PD-L1 cells [TC]≥25%) received (10 mg/kg Q2W ≤12 m); CONDOR (NCT02319044), 67 TC < 25%) m), 133 D+T (D 20 Q4W, T 1 Q4W [7 doses] then Q12W [2 m) VENTANA PD-L1 (SP263) Assay determined status. Paired FFPE archival PBMC samples (as control) the trials evaluated by whole exome sequencing (WES). Tumor mutation burden...
<h3>Background</h3> The phase III DANUBE study assessed the efficacy of PD-L1 inhibitor durvalumab (D), alone or in combination with CTLA-4 tremelimumab (T), versus standard care chemotherapy (SoC) for first-line treatment unresectable, locally advanced metastatic UC. did not meet its co-primary endpoints improving overall survival (OS) D monotherapy vs SoC patients high tumor expression D+T intention-to-treat population.<sup>1</sup> TMB measurement blood (bTMB) tumour (tTMB) has been linked...
Abstract PD-L1 expression by immunohistochemistry (IHC) has proven to be a useful biomarker in determining patient response anti-PD-1/PD-L1-directed therapeutics several cancers, including HNSCC. Understanding the impact of sample type and demography on will inform suitability tumor biopsies for testing. Patients entering HAWK CONDOR studies were screened (n=669) tissue using Ventana SP263 IHC assay as part inclusion criteria. assessment was performed centrally fully validated test...
<div>AbstractPurpose:<p>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.</p>Patients Methods:<p>Tumor samples from HAWK/CONDOR (<i>N</i> = 153) blood 247) were...