Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

IMCISION DNAseq

ABSTRACT: Standard-of-care (SOC) surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) is intensive and results in 30Ã¢Â€Â’50% five-year overall survival. Anti-PD1 immune checkpoint blockade (ICB) durably improves survival rates in recurrent/metastatic HNSCC. We report on the non-randomized phase Ib/IIa IMCISION trial (NCT03003637) of 32 HNSCC patients treated with two doses neoadjuvant nivolumab (NIVO MONO, n=6, phase Ib arm A) or two doses of nivolumab plus a single dose of ipilimumab (COMBO, n=26, 6 in phase Ib arm B and 20 in phase IIa) prior to surgery and, if indicated, adjuvant radiotherapy. Neoadjuvant ICB was feasible in all phase Ib patients, meeting the phase Ib primary feasibility endpoint. One phase IIa patient had progressive disease precluding surgery. Primary tumor pathological response (phase IIa primary endpoint), defined as the % change in viable tumor cells from baseline biopsy to on-treatment resection, was evaluable in 29 patients. . We observed a major pathological response (MPR, 90Ã¢Â€Â’100% response) in 8/23 (35%) evaluable COMBO and 1/6 (17%) NIVO MONO patients. None of the patients with MPR after NIVO MONO or COMBO developed a tumor relapse after 24.0 months median follow-up. FDG-PET-based total lesion glycolysis identified MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia signature expression were observed in MPR patients. Our data indicate that neoadjuvant NIVO MONO and COMBO are safe in HNSCC, and that particularly COMBO ICB shows encouraging effectivity. IMCISION provides rationales for future HNSCC trials aiming to pre-operatively select patients with a likely MPR after neoadjuvant ICB for de-escalation of SOC.

PROVIDER: EGAS00001005466 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Similar Datasets

Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study

Project description:Neoadjuvant immune checkpoint blockade (ICB) has shown unprecedented activity in mismatch repair deficient (MMRd) colorectal cancers, but its effectiveness in MMRd endometrial cancer (EC) remains unknown. In this investigator-driven, phase I, feasibility study (NCT04262089), 10 women with MMRd EC of any grade, planned for primary surgery, received two cycles of neoadjuvant pembrolizumab (200 mg IV) every three weeks. All patients completed treatment without severe toxicity. A partial radiologic response was observed in 3/10 patients, 5/10 patients had stable disease and 2/10 patients were non-evaluable on Magnetic Resonance Imaging (MRI). Pathologic response was observed in 5/10 patients, with 2 patients showing a major pathologic response. No patient achieved a complete pathologic response. At median duration of follow-up of 22.5 months, two non-responders experienced disease recurrence. Monoclonal T cell expansion significantly correlated with treatment response. Tumour-draining lymph nodes displayed clonal overlap with intra-tumoural T cell expansion. All pre-specified endpoints were reached. Neoadjuvant ICB with pembrolizumab proved safe and induced pathologic, radiologic, and immunologic responses in MMRd EC, warranting further exploration of extended neoadjuvant treatment.

2024-07-19 | GSE268903 | GEO

Systemic LRG1 expression in melanoma is associated with disease progression and recurrence

Project description:Treatment of late-stage melanoma patients with immune checkpoint blockade (ICB) is currently one of the most effective standard therapies. The response rates upon neoadjuvant ICB in stage III melanoma are higher as compared to stage IV disease. Given that successful ICB depends on systemic immune response, we hypothesized that systemic immune suppression might be a mechanism responsible for lower response rates in late-stage disease, and also potentially with disease recurrence in early-stage disease.

2024-01-09 | PXD040399 | Pride

Immunologic and clinical activity to ICB combinations in DAPPER Leiomyosarcoma cohort

Project description:Non-inflamed (cold) tumors such as leiomyosarcoma (LMS) do not benefit from immune checkpoint blockade (ICB) monotherapy. Combining ICB with angiogenesis-, or poly-ADP ribose polymerase (PARP) inhibitors may increase tumor immunogenicity by altering the immune cell composition of the tumor microenvironment (TME). The DAPPER phase II study evaluated the safety, immunologic, and clinical activity of ICB-based combinations in pre-treated LMS patients.

2024-01-01 | E-MTAB-12922 | biostudies-arrayexpress

Assessment of tumor pathological and transcriptional biomarkers in pre- and on-treatment core biopsies predictive of response and outcome after neoadjuvant chemotherapy plus Bevacizumab in patients with HER2-negative breast cancer

Project description:Assessment of tumor pathological and transcriptional biomarkers in pre- and on-treatment core biopsies predictive of response and outcome after neoadjuvant chemotherapy plus Bevacizumab in patients with HER2-negative breast cancer: Results from a multi-center, single-arm, phase 2 study (the PROMIX trial) Global gene expression profiling was performed on samples from 3 time points (baseline, after 2 cycles and surgery) from women with breast cancer receivcing neoadjuvant chemotherapy with bevacizumab in a phase 2 trial

2017-09-01 | GSE87455 | GEO

Activity of afatinib in a window pre-operative EORTC study in patients with squamous cell carcinoma of the head and neck (HNSCC)

Project description:Afatinib is a pan-HER inhibitor that improved progression-free-survival (PFS) in recurrent HNSCC versus methotrexate: median PFS 2.6 versus 1.7 months (LUX H&N 1 trial). This study is a translational research linked to EORTC 90111 afatinib trial, an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve HNSCC patients selected for primary curative surgery were randomized (5:1 ratio) to receive Afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumour biopsies, FDG/PET, and MRI were performed at diagnosis and at surgery. The primary end point was metabolic FDG-PET/CT response, defined according to EORTC guidelines.

2019-01-23 | GSE101491 | GEO

Intra-tumoural Microbiota Remodels the Tumour Immune

Project description:Esophageal squamous cell carcinoma (ESCC) accounts for ~90% of all cases of esophageal cancer and the sixth most common cause of cancer related death worldwide. 1, 2 It remains a globally challenging disease and mostly diagnosed cases requires a multidisciplinary approach with extensive treatments including surgery, chemoradiotherapy and/or chemotherapy. ESCC has a relatively high tumor mutational burden,3 suggesting that it could benefit from PD-1 blockade. Recently, three phase III clinical trials reported that PD-1 blockade significantly improved progression-free survival (PFS) and overall survival (OS) when combined with chemotherapy as first-line therapy in advanced/metastatic ESCC.4, 5 Moreover, in 2021 ASCO annual meeting, two phase II clinical trials reported that neoadjuvant chemo-immunotherapy (NACI) induced an obvious improvement of the pathologic complete response (pCR) for resectable ESCC (35. 3% and 42.5%, respectively). Several phase III trials on this topic are ongoing (NCT04807673, NCT04848753, NCT04280822) (https://clinicaltrial s.gov/ct2/show/NCT04807673), indicating that neoadjuvant NACI would become promising treatment for locally advanced ESCC. Nevertheless, not all ESCC patients could respond to NACI. Patients who responded well or poorly to neoadjuvant immunotherapy were treated with surgery. We collected samples from these patients and conducted single-cell sequencing to analyze the tumor immune microenvironment of patients with different therapeutic effects, compare the differences in immune cell composition in the immune microenvironment, and explore more effective neoadjuvant therapy methods.

2023-07-07 | GSE203115 | GEO

Neoadjuvant immune checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/trunk undifferentiated pleomorphic sarcoma (NCT03307616)

Project description:Recent evidence suggests that immune checkpoint blockade (ICB) has some activity in metastatic dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS). We conducted a randomized, non-comparative phase 2 trial (NCT03307616) of nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n=17) and extremity/truncal UPS (n=10), with UPS patients receiving concurrent radiation therapy. The primary endpoint of pathologic response as assessed by percent hyalinization was observed to be a median of 8.8% in DDLPS patients and 89% in UPS patients and similar in nivolumab and ipilimumab/nivolumab arms in both cohorts . Higher intratumoral densities of T-regulatory cells were associated with absence of pathologic response (hyalinization<30%). Tumor infiltration by B-cells was associated with higher densities of T-regulatory cells before treatment; this association was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB with concurrent radiation may have significant efficacy in UPS and is associated complex immune changes in the tumor microenvironment in DDLPS and UPS.

2024-01-01 | GSE202361 | GEO

Implementing whole genome array for clinical use in academic centers: A randomized trial comparing neoadjuvant standard chemotherapy to genomic-driven chemotherapy in operable breast cancer (REMAGUS04 trial)

Project description:REMAUS04 is a phase III trial comparing DNA array-based chemotherapy (by DLD30 score and TOP2A expression) to standard neoadjuvant chemotherapy, in patients with HER2-negative breast carcinoma not eligible for conserving surgery. We evaluated whether whole genome array approach is feasible in daily practice, and if the use of a genomic score (DLD30/TOP2A) improves chemotherapy efficacy.

2016-07-01 | GSE63471 | GEO

Phase II Clinical and Immune Correlate Study of Adjuvant Nivolumab plus Ipilimumab for High-Risk Resected Melanoma

Project description:Background: Adjuvant therapy for high-risk resected melanoma with PD-1 blockade results in median relapse-free survival (RFS) of 5 years. The addition of low dose ipilimumab (IPI) to a regimen of nivolumab (NIVO) in Checkmate-915, did not result in increased RFS. A pilot phase II adjuvant study of either standard or low dose IPI with NIVO was conducted at two centers to evaluate RFS with correlative studies. Methods: Patients (pts) with resected stages IIIB/IIIC/IV melanoma received either IPI 3mg/kg and NIVO 1mg/kg (cohort 4) or IPI 1mg/kg and NIVO 3mg/kg (cohorts 5 and 6) induction therapy every three weeks for 12 weeks, followed by maintenance NIVO. Peripheral blood samples at baseline and on-treatment were assessed by flow cytometry for potential biomarkers. Peripheral CD8+ T-cells were assessed by RNA-Seq. Results: High rates of grade 3-4 adverse events precluded completion of induction therapy in 50%, 35% and 7% of patients in cohorts 4, 5 and 6 respectively. At a median of 63.9 months of follow up, 16/56 pts (29%) relapsed. For all patients, at five-years, RFS was 71% (95% CI: 60, 84), and overall survival was 94% (95% CI: 88, 100). Expansion of CD3+CD4+CD38+CD127-GARP- T-cells, an on-treatment increase in CD39 expression in CD8+ T-cells, and T-cell expression of phosphorylated STAT2 and STAT5 were associated with relapse. Conclusions: Adjuvant IPI/NIVO at the induction doses used resulted in excellent relapse-free survival, albeit with a high rate of grade 3-4 adverse events. Biomarker analyses highlight an association of ectoenzyme-expressing T-cells and STAT signaling pathways with relapse.

2022-12-02 | GSE219251 | GEO

Blockade of LAG-3 and PD-1 leads to co-expression of cytotoxic and exhaustion gene modules in CD8+ T cells to promote antitumor immunity

Project description:Relatlimab (rela; anti-LAG-3) plus nivolumab (nivo; anti-PD-1) is safe and effective for treatment of advanced melanoma. We designed a trial (NCT03743766) where advanced melanoma patients received rela, nivo, or rela+nivo to interrogate the immunologic mechanisms of rela+nivo. Analysis of biospecimens from this ongoing trial demonstrated that rela+nivo led to enhanced capacity for CD8+ T cell receptor signaling and altered CD8+ T cell differentiation, leading to heightened cytotoxicity despite the retention of an exhaustion profile. Co-expression of cytotoxic and exhaustion signatures was driven by PRDM1, BATF, ETV7, and TOX. Effector function was upregulated in clonally expanded CD8+ T cells that emerged after rela+nivo. A rela+nivo intratumoral CD8+ T cell signature was associated with a favorable prognosis. This intratumoral rela+nivo signature was validated in peripheral blood as an elevated frequency of CD38+TIM3+CD8+ T cells. Overall, we demonstrated that cytotoxicity can be enhanced despite the retention of exhaustion signatures, which will inform future therapeutic strategies.

2024-08-11 | GSE225063 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data