Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma

ABSTRACT: We conducted a randomized phase II study of neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients with high-risk resectable melanoma (NCT02519322) and assessed clinical responses and immune correlates. Treatment with combined ipilimumab and nivolumab yielded high response rates (RECIST overall response rate 73%, pathologic complete response rate 45%) but substantial toxicity (73% grade 3 treatment related adverse events), whereas treatment with nivolumab monotherapy yielded modest responses (RECIST overall response rate 25%, pathologic complete response rate 25%) and low toxicity (8% grade 3 treatment related adverse events). Immune correlates of response were identified, demonstrating higher lymphoid infiltrates in responders to both therapies and a more clonal and diverse T cell infiltrate in responders to nivolumab monotherapy. Mutational load was also higher in responders to therapy.

PROVIDER: EGAS00001003178 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Similar Datasets

Biopsies from advanced melanoma before and/or after treatment with nivolumab

Project description:Expression profiling of tumor samples obtained during CA209-038 (ClinicalTrials.gov Identifier: NCT01621490). The purpose of this study is to evaluate pharmacodynamic changes of nivolumab and nivolumab in combination with ipilimumab treatment on the biomarkers measured in the peripheral blood and tumor tissues of subjects with advanced melanoma (unresectable or advanced). Samples are rumor core needle biopsies obtained at trial enrolment (i.e. Screen) and/or at Cycle 1 Day 29 (i.e.Week 4) from Subjects With Advanced Melanoma (Unresectable or Metastatic) treated with nivolumab (BMS-936558,MDX-1106) 3 mg/kg solution intravenously every 2 weeks on Bristol-Myers Squibb clinical trial protocol CA209-038 Part 1 . Cohort 2 patients have progressed on anti-CTLA4 (ipilimumab) monoclonal antibody therapy. Values are from an interim lock of the trial data in July 2014. Best overall response (BOR) was defined using RECIST 1.1 criteria: tumor assessments between date of first dose and the date of first objectively documented progression, or the date of non-missing subsequent anti-cancer therapy (whichever occurs first) were used to derive BOR. MPCT is Maximum reduction in tumor size (index lesions only) up to first progression, and is the value typically shown on a waterfall plot.

2022-01-01 | E-MTAB-4030 | biostudies-arrayexpress

Differential T-cell and monocyte responses in hepatocellular carcinoma treated with regorafenib plus nivolumab: an integrated clinical and biomarker analysis of the phase 2 RENOBATE trial

Project description:Regorafenib has anti-tumor activity in patients with unresectable hepatocellular carcinoma (uHCC) with potential immunomodulatory effects, suggesting that its combination with immune checkpoint inhibitor may have clinically meaningful benefits in patients with uHCC. The multicenter, single-arm, phase 2 RENOBATE trial tested regorafenib-nivolumab as front-line treatment for uHCC. Forty-two patients received nivolumab 480 mg every 4 weeks and regorafenib 80 mg daily (3-weeks-on/1-week-off schedule). The primary endpoint was the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). ORR per RECIST version 1.1 was 31.0%, meeting the primary endpoint. The most common adverse events were palmar-plantar erythrodysesthesia syndrome (38.1%), alopecia (26.2%) and skin rash (23.8%). Median PFS was 7.38 months. The 1-year OS rate was 80.5%, and the median OS was not reached. Exploratory single-cell RNA sequencing analyses of peripheral blood mononuclear cells showed that long-term responders exhibited T cell receptor repertoire diversification, enrichment of genes representing immunotherapy responsiveness in MKI67+ proliferating CD8+ T cells and a higher probability of M1-directed monocyte polarization. Our data support further clinical development of the regorafenib-nivolumab combination as front-line treatment for uHCC and provide preliminary insights on immune biomarkers of response. ClinicalTrials.gov identifier: NCT04310709 .

2023-12-31 | GSE243572 | GEO

Clinical efficacy and biomarker analysis of dual PD-1/CTLA-4 blockade in recurrent/metastatic EBV-associated nasopharyngeal carcinoma

Project description:In this single arm non-randomized phase II trial, 40 patients with recurrent/metastatic EBV-positive nasopharyngeal carcinoma who failed prior chemotherapy received nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks. The best overall objective response rate was 38% with a median progression-free and overall survival of 5.3 and 19.5 months, respectively. This regimen was well-tolerated and treatment-related adverse events requiring discontinuation were low. There was no correlation of response with PD-L1 expression or tumor mutation burden, however patients with low plasma circulating EBV-DNA titre (<7,800 IU/ml) showed a trend to better response and progression-free survival. Deep immunophenotyping of pre- and on-treatment tumor biopsies demonstrated early activation of the adaptive immune response, with T-cell cytotoxicity seen in responders prior to any clinically evident response. Profiling immune-subpopulations also identified a specific PD-1 and CTLA-4 expressing CD8 subpopulation that predicted for response to combined immune checkpoint blockade in nasopharyngeal carcinoma.

2023-04-13 | GSE224450 | GEO

Cyotoxicity in CD8+ T cells differs among adjuvant immune checkpoint blockade therapies

Project description:While immune checkpoint blockade therapies are commonly utilized during the course of metastatic cancer treatment, much remains unknown regarding the mechanisms underlying individual therapies. CD8+ T cells from 8 patients that had been treated with either adjuvant Ipilimumab or Nivolumab were compared to assess immunological differences between the therapies. CD8+ T cells from patients that had received Ipilimumab exhibited higher cytotoxic gene expression and pathway enrichment than those from patients that had received Nivolumab. Cytotoxic activity was especially driven by cluster 3 in both groups, with the proportion of CD8+ T cells in the cluster expanding significantly in Ipilimumab patients over the course of treament, in contrast to Nivolumab patients where this pattern was not seen. This data suggests that, on the CD8+ T cell level, Ipilimumab and Nivolumab exhibit mechanistic differences that are driven by cytotoxic genes and pathways.

2024-10-24 | GSE268364 | 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

Radiation Therapy Inhances Immunotherapy Response in Microsatellite-stable Colorectal and Pancreatic Adenocarcinoma in a Phase II Trial

Project description:Immune checkpoint blockade has limited efficacy in microsatellite stable (MSS) colorectal (CRC) and pancreatic (PDAC) cancer. Preclinical models have demonstrated the use of radiation to activate the innate immune response and stimulate responsiveness to immune checkpoint blockade. Here, we describe a Phase 2 trial of radiation therapy combined with combined anti-CTLA4 (ipilimumab) and anti-PD1 (nivolumab) antibodies in MSS CRC and PDAC. In the per protocol analysis disease control rate was 37% (10/27) in CRC and 29% (5/17) in PDAC with an overall response rate of 15% (4/27) and 18% (3/17), respectively. Whole exome and RNA sequencing of biopsies from 17 patients revealed low tumor mutational burden in all tumors, but a notable upregulation of interferon stimulated genes with concordant high expression of multiple repeat RNA transcripts in responders. Altogether, this study provides foundational human proof of concept of radiation with combination immune checkpoint blockade therapy in otherwise immunotherapy resistant cancers.

2021-07-06 | GSE179351 | GEO

A Study of Nivolumab, Nivolumab Plus Ipilimumab, or Investigator’s Choice Chemotherapy for the Treatment of Participants With Deficient Mismatch Repair (dMMR)/Microsatellite Instability High (MSI-H) Metastatic Colorectal Cancer (mCRC)

Project description:The main purpose of this study is to compare the clinical benefit, as measured by Progression-Free Survival (PFS), Objective Response Rate (ORR), and Overall Survival (OS), achieved by nivolumab in combination with ipilimumab or by nivolumab monotherapy in participants with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) metastatic colorectal cancer (mCRC). This study will also compare nivolumab plus ipilimumab combination vs chemotherapy for treatment of MSI-H/dMMR mCRC participants.

| 2310012 | ecrin-mdr-crc

Capturing the dynamic interactions between tumor and immune components of the tumor micro-environment is important for determining efficacy of anti-PD1 treatment [Post Culture_Metadata]

Project description:RNA extracted from the post 72 hour cultured tumor samples from 31 patients with head and neck squamous cell carcinoma treated Nivolumab and Nivolumab+Ipilimumab was analyzed on the nCounter system using the Pan cancer IO360 panel.

2024-01-09 | GSE234136 | GEO

Mechanisms of response and resistance to combined decitabine and ipilimumab for advanced myeloid disease

Project description:The ETCTN 10026 study tested decitabine and ipilimumab for transplant-naive advanced myelodysplastic syndrome/acute myeloid leukemia and relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Using single cell RNA sequencing, determinants of response (higher T/NK to myeloid cell ratio in responders) and resistance (insufficient clearance of AML clones) were identified and pharmacodynamics of decitabine (cytoreduction) and ipilimumab (increase in regulatory T cells) characterized.

2023-10-31 | GSE223844 | GEO

A multicenter phase II study of Nivolumab monotherapy in recurrent and/or metastatic gastrointestinal cancer patients with high Tumor Mutation Burden (TMB-H)

Project description:Interventions: Monotherapy with Nivolumab 360 mg, every 3 weeks intravenous administration Primary outcome(s): Objective response rate (ORR) determined by RECIST v1.1 Study Design: Single arm Non-randomized

| 2648298 | ecrin-mdr-crc

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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