Author of

• 17556

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  P2.03a - Poster Session with Presenters Present (ID 464)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 17559

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    P2.03a-003 - Belinostat in Combination with Carboplatin and Paclitaxel in Patients with Chemotherapy-Naive Metastatic Lung Cancer (NSCLC) (ID 5996)

    14:30 - 14:30  |  Author(s): T. Song
    • Abstract

    Background:
    Belinostat is a potent inhibitor of the enzyme histone deacetylase (HDAC), which influences chromatin accessibility through altering acetylation levels of histone and non-histone proteins. Belinostat may enhance the antitumor activity of carboplatin and paclitaxel. We conducted a phase 1 clinical trial of belinostat in combination with carboplatin and paclitaxel in chemotherapy-naive patients with stage IV NSCLC.
    
    Methods:
    This was a multicenter phase 1 open label study of belinostat in combination with carboplatin and paclitaxel in chemotherapy-naïve patients with histologically or cytologically confirmed Stage IV NSCLC, PS 0-1. A standard 3+3 dose escalation design was used to determine the primary endpoint of maximum tolerated dose (MTD) of belinostat administered intravenously on days 1-5 of a 21 day cycle in combination with carboplatin (AUC 6) and paclitaxel 200mg/m2 intravenously on day 3 of each cycle for up to 6 cycles. MTD was defined as the dose at which fewer than 2 of 6 patients experienced protocol defined dose-limiting toxicities (DLT) during cycle 1. Maintenance belinostat was allowed after sponsor approval. The starting dose of belinostat was 1000mg/m2. Secondary endpoints were safety and tolerability, progression free survival (PFS) and objective response rate (ORR) of the combination regimen.
    
    Results:
    Twenty three patients were enrolled and treated at the following belinostat levels: 1000 mg/m2 (n=5), 1200 mg/m2 (n=6), 1400 mg/m2 (n=6), 1600 mg/m2 (n=6). At the dose of 1600 mg/m2, 2 of 6 patients experienced DLTS (grade 3 syncope and grade 3 hypotension) and 1400 mg/m2 was determined as the belinostat MTD. Median cycles of belinostat: 10, 7, 5.5 and 4, median cycles of chemotherapy 6, 6, 5.5 and 4 in each of the four cohorts respectively. The most frequent adverse events (all grades) were fatigue (91%), nausea (78%), constipation (74%) anemia and diarrhea (65%) alopecia, arthralgia, decreased appetite, insomnia and neutropenia (61%) dizziness and vomiting (57%) and headache (52%). Median PFS was 5.7 months (95% CI: 2.8, 8.8). 13/23 patients had available response data at the end of cycle 6 with ORR of 35%. The responses observed were partial response in 8 patients (35%), stable disease in 4 patients (17%) and progressive disease in 1 patient (4%). Two patients with partial response at cycle 6 continued on belinostat maintenance and later achieved a complete response.
    
    Conclusion:
    The combination of belinostat and carboplatin and paclitaxel is feasible with observed toxicities consistent with expected side effect profile. Preliminary antitumor activity of this combination was also demonstrated.