Kevin J. Harrington
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View article: Subcutaneous amivantamab in recurrent/metastatic head and neck squamous cell cancer after disease progression on checkpoint inhibitor and chemotherapy: Preliminary results from the phase 1b/2 OrigAMI-4 study
Subcutaneous amivantamab in recurrent/metastatic head and neck squamous cell cancer after disease progression on checkpoint inhibitor and chemotherapy: Preliminary results from the phase 1b/2 OrigAMI-4 study Open
Overexpression of EGFR and MET occurs in a high proportion of recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Amivantamab, an EGFR-MET bispecific antibody with immune-cell directing activity, is approved in…
View article: Second-event endpoints (EFS2, PRFS2 and PFS2) after anti-PD-(L)1-based RCTs: a systematic review and meta-analysis
Second-event endpoints (EFS2, PRFS2 and PFS2) after anti-PD-(L)1-based RCTs: a systematic review and meta-analysis Open
Background Immune checkpoint inhibitors (ICIs), particularly anti-PD-(L)1s, have transformed cancer care by their extended efficacy, even receiving next-line. Event-free survival 2 (EFS2), progression/recurrence-free survival 2 (PRFS2) and…
View article: Developing a therapeutic elastase that stimulates anti-tumor immunity by selectively killing cancer cells
Developing a therapeutic elastase that stimulates anti-tumor immunity by selectively killing cancer cells Open
Recent clinical studies highlight the effectiveness of combining cytotoxic agents with immunotherapies, emphasizing the need for next-generation treatments that integrate both therapeutic approaches. Here, we use 30 cancer cell lines, 15 t…
View article: Xevinapant plus Chemoradiotherapy Negatively Sculpts the Tumor-Immune Microenvironment in Head and Neck Cancer
Xevinapant plus Chemoradiotherapy Negatively Sculpts the Tumor-Immune Microenvironment in Head and Neck Cancer Open
Xevinapant is an orally bioavailable antagonist of select members of the inhibitor of apoptosis protein family. Despite promising phase II data, combining xevinapant with chemoradiotherapy (CRT) failed to improve outcomes in the phase III …
View article: Rapid expansion of podoplanin-positive fibroblasts following radiation limits the anti-tumour CD8+ T-cell response to radiotherapy
Rapid expansion of podoplanin-positive fibroblasts following radiation limits the anti-tumour CD8+ T-cell response to radiotherapy Open
Radiotherapy is known to cause changes in the tumour stroma which can undermine treatment efficacy. Our understanding of this process has historically centred around effects driven by Transforming Growth Factor-beta (TGF-β) and alpha-smoot…
View article: Health-related quality of life outcomes from KEYNOTE-412: chemoradiotherapy with or without pembrolizumab in participants with head and neck squamous cell carcinoma
Health-related quality of life outcomes from KEYNOTE-412: chemoradiotherapy with or without pembrolizumab in participants with head and neck squamous cell carcinoma Open
Background The health-related quality of life (HRQoL) of patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC) is impacted by both disease- and treatment-related factors. Treatments that preserve and maximize HRQo…
View article: Clinical Utility of Whole-Genome Sequencing to Aid Histologic Diagnosis and to Direct Personalized Medicine in Salivary Gland Cancer
Clinical Utility of Whole-Genome Sequencing to Aid Histologic Diagnosis and to Direct Personalized Medicine in Salivary Gland Cancer Open
PURPOSE Salivary gland cancers (SGCs) are rare and comprise multiple histologic entities. In the recurrent or metastatic (R/M) setting, there is limited evidence for effective systemic anticancer treatment for most subtypes, affecting prog…
View article: Electronic pulse device deters and delays shark feeding in a depredation context
Electronic pulse device deters and delays shark feeding in a depredation context Open
Fishers losing their catch or gear to marine predators (‘depredation’), including sharks, is a growing problem around the world. Several types of devices have been tested to deter sharks from engaging in depredation but with limited succes…
View article: Xevinapant or Placebo Plus Platinum-Based Chemoradiotherapy in Unresected Locally Advanced Squamous Cell Carcinoma of the Head and Neck (TrilynX): A Randomized, Phase III Study
Xevinapant or Placebo Plus Platinum-Based Chemoradiotherapy in Unresected Locally Advanced Squamous Cell Carcinoma of the Head and Neck (TrilynX): A Randomized, Phase III Study Open
PURPOSE TrilynX was a randomized, double-blind, phase III study evaluating the addition of xevinapant (an inhibitor of apoptosis proteins inhibitor) or placebo to chemoradiotherapy (CRT) in patients with unresected locally advanced squamou…
View article: Addition of oncolytic virotherapy to clinical isolated limb perfusion for melanoma and sarcoma activates antitumor immunity
Addition of oncolytic virotherapy to clinical isolated limb perfusion for melanoma and sarcoma activates antitumor immunity Open
Background We previously showed that oncolytic virotherapy delivered by isolated limb perfusion (ILP), combined with immune checkpoint inhibition, prevents both local tumor progression and systemic metastases in an animal sarcoma model. Me…
View article: ARID1A stabilizes non-homologous end joining factors at DNA breaks induced by the G4 ligand pyridostatin
ARID1A stabilizes non-homologous end joining factors at DNA breaks induced by the G4 ligand pyridostatin Open
ARID1A, a subunit of the BAF chromatin remodeler, is frequently mutated in cancer. Predicting how ARID1A loss impacts cancer therapy response is challenging because it influences many cellular pathways. G quadruplex (G4) binding ligands, s…
View article: Randomized clinical efficacy and safety study of peltopepimut-S plus cemiplimab compared to cemiplimab alone in patients with recurrent/metastatic HPV16-positive head and neck cancer
Randomized clinical efficacy and safety study of peltopepimut-S plus cemiplimab compared to cemiplimab alone in patients with recurrent/metastatic HPV16-positive head and neck cancer Open
Background Peltopepimut-S is a therapeutic vaccine, which induces specific expansion of both CD4+helper and CD8+cytotoxic T-cells against human papillomavirus type 16 (HPV16) E6/E7 oncoproteins. Patients and methods In a randomized phase 2…
View article: Association of quality of life with mortality in patients with adenoid cystic carcinoma using an internationally-validated QoL questionnaire (EQ-5D-5L)
Association of quality of life with mortality in patients with adenoid cystic carcinoma using an internationally-validated QoL questionnaire (EQ-5D-5L) Open
For patients with ACC, a worse QoL as measured by EQ-5D-5L was associated with a significantly increased risk of death. It remains unclear if poorer QoL has a causal relationship with mortality.
View article: Tumor control and immune activation through palliative irradiation and ATR inhibition, PATRIOT Part C: a phase Ib trial
Tumor control and immune activation through palliative irradiation and ATR inhibition, PATRIOT Part C: a phase Ib trial Open
Ataxia telangiectasia and Rad3-related kinase (ATR) is a rational radiosensitization target. In this study, we explore the combination of the ATR inhibitor, ceralasertib, and palliative radiotherapy, with primary endpoint the identificatio…
View article: Normal tissue outlining guidelines development for soft tissue sarcoma of the extremities
Normal tissue outlining guidelines development for soft tissue sarcoma of the extremities Open
Our results identify that the new NT outlining guidance for STSE is reproducible between observers and within a multi-professional environment, with consistent RTT and RO scores. This reproducibility is attributed to the use of guidelines.…
View article: The PARP inhibitor talazoparib synergizes with reovirus to induce cancer killing and tumour control in vivo in mouse models
The PARP inhibitor talazoparib synergizes with reovirus to induce cancer killing and tumour control in vivo in mouse models Open
Reovirus type 3 Dearing (RT3D) is an oncolytic, double-stranded RNA virus. To identify potential RT3D drug-viral sensitizer, here we use a high-throughput screen of therapeutic agents and find a PARP-1 inhibitor, talazoparib, as a top hit.…
View article: RP1 Combined With Nivolumab in Advanced Anti–PD-1–Failed Melanoma (IGNYTE)
RP1 Combined With Nivolumab in Advanced Anti–PD-1–Failed Melanoma (IGNYTE) Open
PURPOSE Effective treatment options for melanoma after immune checkpoint blockade failure are limited. RP1 (vusolimogene oderparepvec) is a herpes simplex virus type 1–based oncolytic immunotherapy, here evaluated in combination with nivol…
View article: Supplementary Data 1 from INTERLINK-1: A Phase III, Randomized, Placebo-Controlled Study of Monalizumab plus Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
Supplementary Data 1 from INTERLINK-1: A Phase III, Randomized, Placebo-Controlled Study of Monalizumab plus Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Open
Supplementary material
View article: Data from INTERLINK-1: A Phase III, Randomized, Placebo-Controlled Study of Monalizumab plus Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
Data from INTERLINK-1: A Phase III, Randomized, Placebo-Controlled Study of Monalizumab plus Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Open
Purpose:Treatment options for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) after failure of immune checkpoint inhibitor treatment and platinum-based chemotherapy are limited. Preliminary data suggested that mona…
View article: Gas outflows in two recently quenched galaxies at <i>z</i> = 4 and 7
Gas outflows in two recently quenched galaxies at <i>z</i> = 4 and 7 Open
Outflows are a key element in the baryon cycle of galaxies, impacting their evolution by extracting gas, momentum, and energy and then injecting them into the surrounding medium. The properties of gas outflows provide a fundamental test fo…
View article: LiGeR-HN phase III trials of petosemtamab + pembrolizumab and petosemtamab monotherapy in recurrent or metastatic HNSCC
LiGeR-HN phase III trials of petosemtamab + pembrolizumab and petosemtamab monotherapy in recurrent or metastatic HNSCC Open
Patients with recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC) have limited treatment options and a dismal prognosis, especially when their cancer is resistant to standard treatments like anti-programmed cell death …
View article: International Consensus Guideline on Delineation of the Clinical Target Volumes at Different Dose Levels for Nasopharyngeal Carcinoma (2024 Version)
International Consensus Guideline on Delineation of the Clinical Target Volumes at Different Dose Levels for Nasopharyngeal Carcinoma (2024 Version) Open
Amidst the challenges of diverging practices, a comprehensive consensus guideline has been devised based on updated evidence and collective agreement among international experts. This serves as a practical reference for optimal target cove…
View article: Palbociclib and dsRNA sensor co-operate to enhance anti-cancer effects through ER stress and modulation of immune evasion
Palbociclib and dsRNA sensor co-operate to enhance anti-cancer effects through ER stress and modulation of immune evasion Open
Cytoplasmic pattern recognition receptors (PRR) for double-stranded RNA, such as RIG-I/MDA5, are key mediators of anti-viral responses. Here we screen for synergistic drug-virotherapy combinations and find that the reovirus type III Dearin…
View article: Harmonizing the Gut Microbiome and Cellular Immunotherapies: The Next Leap in Cancer Treatment
Harmonizing the Gut Microbiome and Cellular Immunotherapies: The Next Leap in Cancer Treatment Open
The gut microbiome, a diverse community of microorganisms, plays a key role in shaping the host’s immune system and modulating cancer therapies. Emerging evidence highlights its critical influence on the efficacy and toxicity of cell-based…
View article: ARID1A stabilises non-homologous end joining factors at DNA breaks induced by the G4 ligand pyridostatin
ARID1A stabilises non-homologous end joining factors at DNA breaks induced by the G4 ligand pyridostatin Open
SUMMARY ARID1A is a subunit of the BAF chromatin remodelling complex that is frequently mutated in cancer. It is challenging to predict how ARID1A loss impacts cancer therapy response because it participates in many different cellular path…
View article: INTERLINK-1: A Phase III, Randomized, Placebo-Controlled Study of Monalizumab plus Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
INTERLINK-1: A Phase III, Randomized, Placebo-Controlled Study of Monalizumab plus Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Open
Purpose: Treatment options for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) after failure of immune checkpoint inhibitor treatment and platinum-based chemotherapy are limited. Preliminary data suggested that mon…
View article: Atezolizumab in High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck
Atezolizumab in High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck Open
Importance Treating locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) involves any combination of surgery, radiation, and chemotherapy, followed by routine monitoring for local recurrence or distant metastases. Given…