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Arnkjell Lokke - One of the best experts on this subject based on the ideXlab platform.

  • response spectrum analysis of concrete gravity dams including dam water foundation interaction
    Journal of Structural Engineering-asce, 2015
    Co-Authors: Arnkjell Lokke
    Abstract:

    AbstractA response spectrum analysis (RSA) procedure, which estimates the peak response directly from the earthquake design spectrum, is available for the Preliminary Phase of design and safety evaluation of concrete gravity dams. This analysis procedure includes the effects of dam-water foundation interaction, known to be important in the earthquake response of dams. This paper presents a comprehensive evaluation of the accuracy of this RSA procedure by comparing its results with those obtained from response history analysis (RHA) of the dam modeled as a finite-element system, including dam-water-foundation interaction. The earthquake response of an actual dam to an ensemble of 58 ground motions, selected and scaled to be consistent with a target spectrum determined from a probabilistic seismic hazard analysis for the dam site, was determined by the RHA procedure. The median of the peak responses of the dam to 58 ground motions provided the benchmark result. The peak response was also estimated by the RS...

  • response spectrum analysis of concrete gravity dams including dam water foundation interaction
    Journal of Structural Engineering-asce, 2015
    Co-Authors: Arnkjell Lokke, Anil K Chopra
    Abstract:

    AbstractA response spectrum analysis (RSA) procedure, which estimates the peak response directly from the earthquake design spectrum, is available for the Preliminary Phase of design and safety eva...

Anil K Chopra - One of the best experts on this subject based on the ideXlab platform.

Emmett V Schmidt - One of the best experts on this subject based on the ideXlab platform.

  • epacadostat plus pembrolizumab in patients with advanced rcc Preliminary Phase i ii results from echo 202 keynote 037
    Journal of Clinical Oncology, 2017
    Co-Authors: Omid Hamid, Todd M Bauer, Alexander I Spira, Anthony J Olszanski, Sandip Pravin Patel, Jeffrey S Wasser, David Smith, Ani Sarkis Balmanoukian, Charu Aggarwal, Emmett V Schmidt
    Abstract:

    4515Background: Epacadostat (E) is a potent oral inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan-catabolizing enzyme that induces immune tolerance by T-cell suppression. Preclinical and clinical data suggest that epacadostat has antitumor activity when combined with checkpoint inhibitors, including the PD-1 inhibitor pembrolizumab (P). ECHO-202/KEYNOTE-037 is an ongoing open-label, Phase 1/2 (P1/2) study evaluating E + P in multiple tumor types. We report Preliminary P1/2 efficacy and safety data for the advanced renal cell carcinoma (RCC) cohort as of a 29OCT2016 data cutoff. Methods: Eligible patients (pts) had advanced clear-cell RCC, prior antiangiogenic therapy (tx), and no prior checkpoint inhibitor tx. In P1 dose escalation (3+3+3), pts received E (25, 50, 100, or 300 mg PO BID) + P (2 mg/kg or 200 mg IV Q3W); MTD was not exceeded. E (100 mg BID) + P (200 mg Q3W) dosing was selected for P2 cohort expansion. Response was assessed in RECIST 1.1 evaluable pts. Safety/tolerability was a...

  • epacadostat plus pembrolizumab in patients with advanced urothelial carcinoma Preliminary Phase i ii results of echo 202 keynote 037
    Journal of Clinical Oncology, 2017
    Co-Authors: David Smith, Omid Hamid, Anthony J Olszanski, Sandip Pravin Patel, Jeffrey S Wasser, Emmett V Schmidt, Thomas F Gajewski, Ronac Mamtani, Yufan Zhao, Janet Maleski
    Abstract:

    4503Background: Pembrolizumab (P), a PD-1 inhibitor, is active and well tolerated in platinum-treated, advanced urothelial carcinoma (UC). Epacadostat (E) potently and selectively inhibits indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan-catabolizing enzyme that suppresses T-cell–mediated immune surveillance. IDO1 overexpression is associated with tumor progression and shortened patient (pt) survival. ECHO-202/KEYNOTE-037 is an open-label, Phase I/II study of E + P in pts with advanced tumors. We report Phase I/II efficacy and safety outcomes for the UC cohort at an October 29, 2016 data cutoff. Methods: Adult pts with advanced UC, prior platinum therapy (adjuvant or advanced disease setting) or alternative therapy (if platinum was not appropriate), and no prior checkpoint inhibitor therapy were eligible to participate. In Phase I, pts received E (25, 50, 100, or 300 mg PO BID) + P (2 mg/kg or 200 mg IV Q3W); MTD was not exceeded. E (100 mg BID) + P (200 mg Q3W) dosing was selected for Phase II. Respons...

Omid Hamid - One of the best experts on this subject based on the ideXlab platform.

  • epacadostat plus pembrolizumab in patients with advanced rcc Preliminary Phase i ii results from echo 202 keynote 037
    Journal of Clinical Oncology, 2017
    Co-Authors: Omid Hamid, Todd M Bauer, Alexander I Spira, Anthony J Olszanski, Sandip Pravin Patel, Jeffrey S Wasser, David Smith, Ani Sarkis Balmanoukian, Charu Aggarwal, Emmett V Schmidt
    Abstract:

    4515Background: Epacadostat (E) is a potent oral inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan-catabolizing enzyme that induces immune tolerance by T-cell suppression. Preclinical and clinical data suggest that epacadostat has antitumor activity when combined with checkpoint inhibitors, including the PD-1 inhibitor pembrolizumab (P). ECHO-202/KEYNOTE-037 is an ongoing open-label, Phase 1/2 (P1/2) study evaluating E + P in multiple tumor types. We report Preliminary P1/2 efficacy and safety data for the advanced renal cell carcinoma (RCC) cohort as of a 29OCT2016 data cutoff. Methods: Eligible patients (pts) had advanced clear-cell RCC, prior antiangiogenic therapy (tx), and no prior checkpoint inhibitor tx. In P1 dose escalation (3+3+3), pts received E (25, 50, 100, or 300 mg PO BID) + P (2 mg/kg or 200 mg IV Q3W); MTD was not exceeded. E (100 mg BID) + P (200 mg Q3W) dosing was selected for P2 cohort expansion. Response was assessed in RECIST 1.1 evaluable pts. Safety/tolerability was a...

  • epacadostat plus pembrolizumab in patients with advanced urothelial carcinoma Preliminary Phase i ii results of echo 202 keynote 037
    Journal of Clinical Oncology, 2017
    Co-Authors: David Smith, Omid Hamid, Anthony J Olszanski, Sandip Pravin Patel, Jeffrey S Wasser, Emmett V Schmidt, Thomas F Gajewski, Ronac Mamtani, Yufan Zhao, Janet Maleski
    Abstract:

    4503Background: Pembrolizumab (P), a PD-1 inhibitor, is active and well tolerated in platinum-treated, advanced urothelial carcinoma (UC). Epacadostat (E) potently and selectively inhibits indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan-catabolizing enzyme that suppresses T-cell–mediated immune surveillance. IDO1 overexpression is associated with tumor progression and shortened patient (pt) survival. ECHO-202/KEYNOTE-037 is an open-label, Phase I/II study of E + P in pts with advanced tumors. We report Phase I/II efficacy and safety outcomes for the UC cohort at an October 29, 2016 data cutoff. Methods: Adult pts with advanced UC, prior platinum therapy (adjuvant or advanced disease setting) or alternative therapy (if platinum was not appropriate), and no prior checkpoint inhibitor therapy were eligible to participate. In Phase I, pts received E (25, 50, 100, or 300 mg PO BID) + P (2 mg/kg or 200 mg IV Q3W); MTD was not exceeded. E (100 mg BID) + P (200 mg Q3W) dosing was selected for Phase II. Respons...

David Smith - One of the best experts on this subject based on the ideXlab platform.

  • epacadostat plus pembrolizumab in patients with advanced rcc Preliminary Phase i ii results from echo 202 keynote 037
    Journal of Clinical Oncology, 2017
    Co-Authors: Omid Hamid, Todd M Bauer, Alexander I Spira, Anthony J Olszanski, Sandip Pravin Patel, Jeffrey S Wasser, David Smith, Ani Sarkis Balmanoukian, Charu Aggarwal, Emmett V Schmidt
    Abstract:

    4515Background: Epacadostat (E) is a potent oral inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan-catabolizing enzyme that induces immune tolerance by T-cell suppression. Preclinical and clinical data suggest that epacadostat has antitumor activity when combined with checkpoint inhibitors, including the PD-1 inhibitor pembrolizumab (P). ECHO-202/KEYNOTE-037 is an ongoing open-label, Phase 1/2 (P1/2) study evaluating E + P in multiple tumor types. We report Preliminary P1/2 efficacy and safety data for the advanced renal cell carcinoma (RCC) cohort as of a 29OCT2016 data cutoff. Methods: Eligible patients (pts) had advanced clear-cell RCC, prior antiangiogenic therapy (tx), and no prior checkpoint inhibitor tx. In P1 dose escalation (3+3+3), pts received E (25, 50, 100, or 300 mg PO BID) + P (2 mg/kg or 200 mg IV Q3W); MTD was not exceeded. E (100 mg BID) + P (200 mg Q3W) dosing was selected for P2 cohort expansion. Response was assessed in RECIST 1.1 evaluable pts. Safety/tolerability was a...

  • epacadostat plus pembrolizumab in patients with advanced urothelial carcinoma Preliminary Phase i ii results of echo 202 keynote 037
    Journal of Clinical Oncology, 2017
    Co-Authors: David Smith, Omid Hamid, Anthony J Olszanski, Sandip Pravin Patel, Jeffrey S Wasser, Emmett V Schmidt, Thomas F Gajewski, Ronac Mamtani, Yufan Zhao, Janet Maleski
    Abstract:

    4503Background: Pembrolizumab (P), a PD-1 inhibitor, is active and well tolerated in platinum-treated, advanced urothelial carcinoma (UC). Epacadostat (E) potently and selectively inhibits indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan-catabolizing enzyme that suppresses T-cell–mediated immune surveillance. IDO1 overexpression is associated with tumor progression and shortened patient (pt) survival. ECHO-202/KEYNOTE-037 is an open-label, Phase I/II study of E + P in pts with advanced tumors. We report Phase I/II efficacy and safety outcomes for the UC cohort at an October 29, 2016 data cutoff. Methods: Adult pts with advanced UC, prior platinum therapy (adjuvant or advanced disease setting) or alternative therapy (if platinum was not appropriate), and no prior checkpoint inhibitor therapy were eligible to participate. In Phase I, pts received E (25, 50, 100, or 300 mg PO BID) + P (2 mg/kg or 200 mg IV Q3W); MTD was not exceeded. E (100 mg BID) + P (200 mg Q3W) dosing was selected for Phase II. Respons...