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A Phase II Trial of Adjuvant Durvalumab following Trimodality Therapy for Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma: A Big Ten Cancer Research Consortium Study

ABSTRACT: Correlative analysis using RNA-seq was performed on tumor samples from patients with locally advanced esophageal and gastroesophageal junction adenocarcinoma treated with adjuvant durvalumab as part of a Phase II trial. The primary goal of this correlative analysis was to perform immune deconvolution using CIBERSORTx in order to determine the relative proportion of immune cell types in each sample. The immune components were then associated with relapse free survival.

ORGANISM(S): Homo sapiens

PROVIDER: GSE183924 | GEO | 2021/09/12

REPOSITORIES: GEO

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A Phase II Trial of Adjuvant Durvalumab following Trimodality Therapy for Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma: A Big Ten Cancer Research Consortium Study

Project description:A Phase II Trial of Adjuvant Durvalumab following Trimodality Therapy for Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma: A Big Ten Cancer Research Consortium Study

| PRJNA762343 | ENA

A Phase II Trial of Adjuvant Durvalumab Following Trimodality Therapy for Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma: A Big Ten Cancer Research Consortium Study.

Project description: Not available

| S-EPMC8484871 | biostudies-literature

Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 platform trial

Project description:Durvalumab with olaparib was one of the experimental regimens evaluated in I-SPY 2, a neoadjuvant platform trial for high risk, early stage breast cancer, and graduated in the HER2- and HR+HER2- signatures. We hypothesized that (pre-treatment) expression-based immune signatures may predict response to the immune checkpoint inhibitor durvalumab and signatures related to DNA repair deficiency (DRD) may associate with response to olaparib. In this analysis, we assessed 13 expression based signatures related to immune, DRD, proliferation and estrogen signaling as specific predictor of pathologic complete response (pCR) to durvalumab/olaparib.

2021-06-10 | GSE173839 | GEO

Neoadjuvant durvalumab plus radiation versus durvalumab alone in stages I-III non-small cell lung cancer: survival outcomes and molecular correlates of a randomized phase II trial

Project description:Randomized phase II trial patients with early-stage non-small cell lung cancer were treated with either two preoperative cycles of the anti-PD-L1 antibody durvalumab alone or combined with immunomodulatory doses of stereotactic radiation. We report, based on transcriptome analyses of resected tumors, a correlation between an increase of immune pathway genes and freedom from recurrence.

2023-11-26 | GSE248378 | GEO

An open-label, phase II basket study of an oral hypomethylating agent CC-486 and durvalumab in advanced solid tumors

Project description:Purpose: To evaluate whether administration of the oral DNA hypomethylating agent (HMA) CC-486 enhances the poor response rate of immunologically ‘cold’ solid tumors to immune checkpoint inhibitor durvalumab.

2020-07-26 | GSE147537 | GEO

Exploring the molecular mechanisms behind the potentiation of chemotherapy effects by durvalumab in lung adenocarcinoma cell lines

Project description:Immune checkpoint inhibitors are increasingly used in combination with chemotherapy for treatment of non-small cell lung cancer, yet the success of combination therapies is relatively limited. Thus, more detailed insight regarding the tumour molecular markers that may affect the responsiveness of patients to therapy is required. Here, we set out to explore the proteome of two lung adenocarcinoma cell lines (HCC-44 and A549) treated with cisplatin, pemetrexed, durvalumab, and the corresponding mixtures to establish the differences in post-treatment protein expression that can serve as markers of chemosensitivity or resistance.

2023-05-12 | PXD040761 | Pride

Expression data from durvalumab, oleclumab and combo-treated xenograft NSCLC tumors

Project description:Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations do not respond to anti-PD-1 (L1) as well as tumors without an EGFR mutation. We showed in a xenograft mouse model of EGFR-mutated NSCLC that, neither durvalumab nor oleclumab alone inhibited tumor growth compared to the isotype control. In contrast, the combination of both antibodies significantly inhibited tumor growth and increased gene expressions that corresponded to inflammation and T cell function in tumors treated. We used microarrays to study gene expressions that corresponded to enhanced immune response in antibody-treated mice.

2022-02-23 | GSE190731 | GEO

Interferon Gamma mRNA Signature in Tumor Biopsies Predicts Outcomes in Patients with Non–Small-Cell Lung Carcinoma or Urothelial Cancer Treated with Durvalumab

Project description:An unmet need in cancer treatment is identification of biomarkers of response to PD-1 or PD-L1 immune checkpoint inhibitors that predict therapeutic outcomes in patients with non–small-cell lung carcinoma (NSCLC) and urothelial cancer (UC). Expression of PD-L1 measured by immunohistochemistry has limited capacity for predicting outcomes of immune checkpoint therapy because expression of this biomarker does not correlate highly with treatment response. In addition, PD-L1 as measured on tumor cells, which has been approved by the FDA for both companion and complementary diagnostic utility, does not necessarily reflect anti-tumor activity of tumor-infiltrating lymphocytes. Results presented in this report demonstrate that gene expression levels of four interferon gamma (IFNγ)-inducible mRNAs correlate with improved clinical outcomes in patients with NSCLC or UC treated with the PD-L1 inhibitor durvalumab. This IFNγ gene signature may augment the predictive value of PD-L1 and other biomarkers in identifying cancer patients most likely to respond to therapy with durvalumab or other immune checkpoint inhibitors.

2018-02-14 | GSE110390 | GEO

Clinical and Biomarker Results from A Phase II Trial of Combined Cabozantinib and Durvalumab in Patients with Chemotherapy-refractory Colorectal Cancer (CRC): CAMILLA CRC Cohort

Project description:CAMILLA is a basket trial (NCT03539822) evaluating cabozantinib plus the ICI durvalumab in chemorefractory gastrointestinal cancer. Herein, are the phase II colorectal cohort results. 29 patients were evaluable. 100% had confirmed pMMR/MSS tumors. Primary endpoint was met with ORR of 27.6% (95% CI 12.7-47.2%). Secondary endpoints of 4-month PFS rate was 44.83% (95% CI 26.5-64.3%); and median OS was 9.1 months (95% CI 5.8-20.2). Grade≥3 TRAE occurred in 39%. In post-hoc analysis of patients with RAS wild type tumors, ORR was 50% and median PFS and OS were 6.3 and 21.5 months respectively. Exploratory spatial transcriptomic profiling of pretreatment tumors showed upregulation of VEGF and MET signaling, increased extracellular matrix activity and pre-existing anti-tumor immune responses coexisting with immune suppressive features like T cell migration barriers in responders versus non-responders. Cabozantinib plus durvalumab demonstrated anti-tumor activity, manageable toxicity, and have led to the activation of the phase III STELLAR-303 trial.

2024-01-27 | GSE254054 | GEO

First-line durvalumab and tremelimumab with chemotherapy in RAS-mutated metastatic colorectal cancer: a phase 1b/2 trial [RNA-Seq]

Project description:While patients with microsatellite instable, metastatic colorectal cancer (CRC) benefit from immune checkpoint blockade, chemotherapy with targeted therapies remains the only therapeutic option for microsatellite stable (MSS) tumors. The single arm, phase IB/II MEDITREME trial evaluates safety and efficacy of durvalumab plus tremelimumab in combination with mFOLFOX6 chemotherapy in first line, in 57 patients with RAS-mutant unresectable mCRC. Safety was primary objective of phase IB and no safety issue was observed. The primary objective of phase II was efficacy in terms of 3-month PFS in MSS patients, which was met with a 3 month PFS of 90.7% [95% CI: 79.2-96%]. For secondary objective, response rate was 64.5%, median PFS was 8.2 months [95% CI: 5.9–8.6] and overall survival was not reached in MSS patients. Higher tumor mutational burden and a lower degree of genomic instability in responder patients. Integrated transcriptomic analysis underlined that high immune signature, and low epithelio-mesenchymal transition were associated with better outcome. Immunomonitoring showed induction of neoantigen and NY-ESO1 and TERT blood tumor specific T cell response associated with better PFS. The combination of durvalumab-tremelimumab with mFOLFOX6 was tolerable with promising clinical activity in MSS mCRC.

2023-07-05 | GSE235919 | GEO

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