Author of

• 20153

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  P1.04 - Clinical Design, Statistics and Clinical Trials (ID 690)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Clinical Design, Statistics and Clinical Trials
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 22621

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    P1.04-012 - A Phase 1b Dose-Escalation Study of TRC105 in Combination with Nivolumab  in Patients with Metastatic Non-Small Cell Lung Cancer (ID 8386)

    09:30 - 09:30  |  Author(s): J. Keef
    • Abstract
    • Slides

    Background:
    Nivolumab (N) has demonstrated clinical benefit in advanced non-small cell lung cancer (NSCLC) patients (PTS) who have progressed to platinum-based chemotherapy: improved overall survival (OS) versus (Vs) docetaxel in squamous NSCLC (median OS of 9.2 months [mo} Vs 6 mo) and in non-squamous NSCLC (median OS of 12.2 mo Vs 9.4 mo). TRC105 is an antibody to endoglin, a receptor expressed on proliferating endothelial cells and myeloid derived suppressor cell (MDSCs). MDSCs also inhibit anti-cancer immunity, but by a mechanism of action that is distinct from that inhibited by N. TRC105 inhibits tumor growth in preclinical models and complements the activity of antibodies that target the programmed death receptor (PD-1). Its toxicity profile is distinct from that of N. By targeting MDSCs, TRC105 has the potential to complement N and improve clinical efficacy over that seen with single agent N.
    
    Method:
    This is a phase 1b,dose-finding (3+3 design) study of TRC105 in combination with standard dose (240mg) of N in pts with advanced NSCLC with disease progression to platinum-containig doublet chemotherapy.The primary objective is to evaluate safety and tolerability and determine a recommended phase 2 dose of TRC105 in combination with standard dose of N. Secondary objectives include: preliminary evidence of antitumor activity by assessing response rate and progression-free survival; characterize the pharmacokinetic profile of TRC105 when given in combination with N; and to explore biologic effects of TRC105 and N on circulating immune cells. Two dose levels of TRC105 are initially considered: Dose Level I: 8mg/kg intravenously (IV) weekly for 4 weeks → 15mg/kg every 2 weeks; Level II: 10mg/kg (iv) for 4 weeks → 15mg/kg every 2 weeks. N will be administered IV every 2 weeks in both cohorts of pts.Toxicity and efficacy assessments will be determine using NCI-CTCAE(V 4) and RECIST (V 1.1),respectively. The dose-limiting toxicity (DLT) evaluation period will be the first 4 weeks of the first cycle of treatment. It is anticipated that up to 18 pts will be enrolled in the study,and up to 12 pts at the maximum tolerated dose(MTD).. Main criteria for inclusion are: confirmed stage 4 NSCLC,prior platinum-based doublets,measurable disease,ECOG PS 0-1,PD-L1 expression >/ 1%,adequate organ function,and no prior therapy with an immuno check point inhibitor. Descriptive statistics will be used to summarize pt characteristics,safety/efficacy/pharmacokinetic parameters ,and immunologic biomarkers.
    
    Result:
    Section not applicable
    
    Conclusion:
    Section not applicable
    
    

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