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  • Citrin, Deborah E.  (3)
  • Duffy, Austin G.  (3)
  • Figg, William Douglas  (3)
  • 1
    Online Resource
    Online Resource
    A pilot study of immune checkpoint inhibition (tremelimumab and/or MEDI4736) in combination with radiation therapy in patients with unresectable pancreatic cancer.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 4_suppl ( 2016-02-01), p. TPS470-TPS470
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 4_suppl ( 2016-02-01), p. TPS470-TPS470
    Abstract: TPS470 Background: Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 expressed on the surface of activated T lymphocytes and causes inhibition of B7-CTLA-4-mediated downregulation of T-cell activation. MEDI4736 is a human monoclonal antibody directed against PD-L1. Blockage of ligation between PD-L1 and PD1 induces local immune activation and prevents anergy and exhaustion of effector T-cells. Several studies have documented an increase in peripheral antitumor immunity following radiation. This effect is evidently too weak to be clinically relevant, but has the potential to be boosted by immune modulation. The underlying hypothesis of this study is that the effect of immune checkpoint inhibition (accomplished via tremelimumab and/or MEDI4736) treatment can be enhanced by radiation in patients with advanced pancreatic carcinoma. Whilst radiation treatment in pancreas cancer is commonly employed in limited or early stage disease, if radiation can enhance the effect of immune checkpoint inhibition to produce systemic anti-tumor effects the combination could become an effective treatment modality for patients with advanced disease. Methods: Patients with histologically confirmed metastatic pancreatic cancer with primary in-situ (or locally-recurrent) disease are being enrolled to this pilot study. The primary objectives are to determine the safety, tolerability and feasibility of immune checkpoint inhibition [comprising either MEDI4736 alone (Cohort A), Tremelimumab (Cohort B) or combined MEDI4736 and Tremelimumab (Cohort C)] in combination with stereotactic body radiation therapy (SBRT) in patients with unresectable pancreatic cancer. Select eligibility criteria are as follows: at least 1 measurable metastatic lesion by RECIST 1.1 criteria and accessible for biopsy. No prior radiation therapy to the pancreas allowed. There is no limit to the number of prior chemotherapy regimens received; ECOG ≤ 1; Life expectancy of greater than 3 months. Acceptable organ and bone marrow function. No active or prior documented autoimmune or inflammatory disorders. Clinical trial information: NCT02311361.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2016.34.4_suppl.tps470
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    A pilot study of immune checkpoint inhibition in combination with radiation therapy in patients with metastatic pancreatic cancer.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. e15786-e15786
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e15786-e15786
    Abstract: e15786 Background: Durvalumab is a human IgG1 monoclonal antibody directed against PD-L1. Tremelimumab is a selective human IgG2 monoclonal antibody against CTLA-4. Several studies have documented an increase in peripheral antitumor immunity following radiation. The hypothesis of this study is that the effect of immune checkpoint inhibition (ICI) can be enhanced by radiation in pancreatic adenocarcinoma (PAC). Methods: Patients with histologically confirmed metastatic PC with primary in-situ or metastatic SBRT-amenable disease are being enrolled to this pilot study. Primary objective to determine safety, tolerability and feasibility of immune checkpoint inhibition [comprising either Durvalumab alone (Cohort A), or combined durvalumab and tremelimumab (Cohort B)] in combination with stereotactic body radiation therapy (SBRT) at two different schedules (8Gy/single fraction or 25Gy in 5 fractions). Select eligibility criteria are as follows: at least 1 measurable metastatic lesion by RECIST 1.1 accessible for biopsy. No limit to the number of prior chemotherapy regimens; ECOG ≤ 1; Life expectancy of greater than 3 months. Acceptable organ and bone marrow function. No active autoimmune disorders. Results: N = 24 patients with chemorefractory metastatic PC have so far been enrolled; M/F = 13/11; Median age = 61. Treatment was well tolerated. No DLT encountered. The most common toxicity was fatigue (G1/2) in all patients in DL2. 5/24 pts had early d iscontinuation ( 〈 4 wks) due to rapid PD. No objective responses have been seen. 5 pts (21%) had SD as best response. Conclusions: Immune checkpoint inhibition in combination with SBRT in advanced pancreatic cancer is safe and feasible. Preliminarily no objective responses have been seen for these schedules of SBRT with durvalumab. The study is continuing with evaluation of SBRT with dual checkpoint inhibition (durvalumab and tremelimumab). Clinical trial information: NCT02311361.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.e15786
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    A pilot study of AMP-224, a PD-L2 Fc fusion protein, in combination with stereotactic body radiation therapy (SBRT) in patients with metastatic colorectal cancer.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 4_suppl ( 2016-02-01), p. 560-560
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 4_suppl ( 2016-02-01), p. 560-560
    Abstract: 560 Background: AMP-224, a PD-L2 Fc fusion protein, binds to PD-1, an inhibitory receptor that is present on the cell surface of exhausted, activated, effector, and memory T cells. AMP-224 has a unique mechanism of action in that it binds specifically to PD-1 HI T cells (chronically stimulated / exhausted T cells) but not PD-1 LO cells which represent the normal activated T cell population. Preclinical studies have documented an increase in antitumor immunity following radiation therapy (RT), but also tumor PD-L1 expression as an escape mechanism. The aim of the study is to evaluate whether inhibition of PD-1/PDL-1 axis could improve anti-tumor immunity effects of RT. Methods: Patients with histologically confirmed metastatic colorectal cancer to liver were treated with SBRT to a site of liver metastasis at 8Gy in a single fraction (DL1) or 8Gy in 3 daily fractions (DL2). All patients received AMP-224 10mg/kg IV beginning Day 1 after SBRT preceded by cyclophosphamide 200mg/m2 (D0). Primary objective was to determine the safety and feasibility of AMP-224 in combination with stereotactic body radiation therapy (SBRT) to metastatic hepatic metastasis in patients with advanced colorectal cancer. Mandatory pre- and post-treatment biopsies were attempted on all patients. Results: N = 17 patients with refractory metastatic CRC were enrolled. N = 2 pts were unevaluable. 6pts were treated at DL1 (8Gy x 1fraction SBRT, AMP-224 10mg/kg q2-weekly) and 9pts were treated at DL2 (8Gy x 3fractions SBRT, AMP-224 10mg/kg q2-weekly) No DLT was encountered. The most common toxicity was fatigue (G1/2) in all patients in DL2. N = 3 patients experienced G2 infusion reaction which responded to standard interventions. 5/15 pts did not complete treatment due to rapid PD. No objective responses have been seen, although N = 6 pts remain on study. Pre- and post-tumor biopsies were performed on 7 of first 11 pts. Conclusions: AMP-224 in combination with SBRT to site of colorectal hepatic metastases is safe and feasible. Preliminarily no objective responses have been seen. Full clinical and correlative data including post-therapeutic radiated and non-radiated tumor biopsies will be presented. Clinical trial information: NCT02298946.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2016.34.4_suppl.560
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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