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  • American Society of Clinical Oncology (ASCO)  (2)
  • 1
    Online Resource
    Online Resource
    Distinct biosignatures associate with survival after chemoimmunotherapy in a randomized, three-arm phase II study in patients with metastatic pancreatic cancer.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 4010-4010
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 4010-4010
    Abstract: 4010 Background: Preclinical and small clinical studies of chemoimmunotherapy for metastatic pancreatic ductal adenocarcinoma (mPDAC) point to a yet unrealized potential of clinically significant immune activation. In our phase II study of the CD40 agonist antibody sotigalimab (sotiga) and/or nivolumab (nivo) with gemcitabine and nab-paclitaxel (chemo), we observed promising improvements in overall survival (OS) in 105 patients with newly diagnosed mPDAC (NCT03214250); the primary endpoint of 1-year OS rate was 57.7% (p = 0.006) in the nivo/chemo arm, 48.1% (p = 0.062) in the sotiga/chemo arm and 41.3% (p = 0.233) in the nivo/sotiga/chemo arm (O’Hara, ASCO 2021) as compared to a historical control of 35%. Here, we report results of multi-omic translational analyses designed to identify signatures predictive of OS benefit. Methods: Longitudinal blood and tumor tissue samples were collected for immune and tumor biomarker analysis. Tumor samples underwent RNA sequencing and multiplex immunofluorescence (mIF). Peripheral blood was analyzed by mass cytometry time of flight (CyTOF), high parameter flow cytometry, and proteomics. Machine learning (ML) algorithms were applied to the data to identify biosignatures related to OS in each arm. Results: Comprehensive multi-omic, multi-parameter immune and tumor biomarker analyses identified distinct pretreatment immune signatures predictive of longer OS specific to nivo/chemo or sotiga/chemo (Table, representative examples). Because patients in each arm received chemotherapy, these and other arm-unique biomarkers suggest a relationship to the immunotherapy rather than chemotherapy in this randomized study. There was evidence of immune exhaustion in the sotiga/nivo/chemo arm that may explain the lack of survival benefit. Conclusions: From in-depth translational and ML analyses of randomized phase II trial of first-line chemoimmunotherapy in mPDAC patients, we identified novel biomarkers that associated with OS distinctly in each arm. Clinical trials in first-line mPDAC exploiting these previously unappreciated biomarkers and aiming to enrich patients for response, are warranted to further advance chemoimmunotherapy in this disease. Clinical trial information: NCT03214250. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.4010
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Phase II study of EZN-2208 (PEG-SN38) with or without cetuximab in patients with metastatic colorectal cancer (CRC).
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 4_suppl ( 2012-02-01), p. 448-448
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 4_suppl ( 2012-02-01), p. 448-448
    Abstract: 448 Background: EZN-2208 is a water-soluble, parenterally-delivered PEGylated conjugate of SN38 that increases solubility, exposure, and apparent half-life of SN-38. Methods: Patients with metastatic or locally recurrent CRC previously treated with fluoropyrimidines, oxaliplatin and irinotecan, and no more than 2 distinct progressions, were screened for K-Ras mutation and stratified accordingly. Patients with K-Ras tumor mutation (Mut) were treated with EZN-2208 (9mg/m 2 SN-38 equivalents) over 1-h IV on days 1, 8, 15 in 4-wk cycles (Arm A). Patients with K-Ras wild type (WT) tumors were randomized (2:1) to EZN-2208 (as above) and cetuximab (250mg/m 2 weekly following 400mg/m 2 on D1) (Arm B) or to irinotecan (125mg/m 2 ) over 90min IV days 1, 8 in 3 week cycles and cetuximab (as above) (Arm C). The primary objectives of the study were to determine the overall response rates (ORR) and progression free survival (PFS) (Arm A) and compare PFS (Arms B and C). A comparison of safety and toxicity of EZN-2208 and irinotecan was planned as well. Results: Demographic and efficacy parameters are summarized in the table . Common adverse events (Arms A%, B%, C%), observed in 〉 25% of patients in at least one arm of the study, were diarrhea (45%, 64%, 55%), fatigue (56%, 56%, 39%), nausea (43%, 59%, 47%), vomiting (31%, 46%, 39%), constipation (27%, 26%, 37%), abdominal pain (25%, 28%, 32%), anemia (33%, 21%, 21%), dermatitis acneiform (0%, 28%, 26%), hypokalemia (17%, 28%, 26%), and alopecia (12%, 28%, 3%). Conclusions: EZN-2208 in combination with cetuximab is active in patients in the 3rd line setting of CRC and comparable to irinotecan in combination with cetuximab. EZN-2208 monotherapy did not result in responses in patients with CRC following progression on irinotecan. EZN-2208 has an acceptable safety and tolerability profile as monotherapy, and in combination with cetuximab. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.4_suppl.448
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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