Author of

• 20203

  +

  P1.01 - Advanced NSCLC (ID 757)

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

  • 22476

    +

    P1.01-070 - BIW-8962, an Anti-GM2 Ganglioside Monoclonal Antibody, in Advanced/Recurrent Lung Cancer: A Phase I/II Study (ID 10421)

    09:30 - 09:30  |  Author(s): N. Shiraishi
    • Abstract

    Background:
    GM2 ganglioside is a tumor-associated antigen that is overexpressed in a high proportion of several malignancies, e.g. SCLC, NSCLC, mesothelioma, melanoma, neuroblastoma, multiple myeloma. BIW-8962 is a recombinant, humanized, non-fucosylated immunoglobulin G1 monoclonal antibody to GM2 ganglioside that shows pre-clinical activity towards lung cancer cell lines and in an animal model bearing SCLC xenografts. The aim of this study was to determine the safety and preliminary clinical efficacy of BIW-8962 administered as monotherapy in patients with previously treated lung cancer.
    
    Method:
    In phase I, patients (N=16) with advanced, recurrent lung cancer (8 each with SCLC and NSCLC) received increasing doses of BIW-8962 (1–10 mg/kg) intravenously every 3 weeks using a standard 3+3 design to determine the maximum tolerated dose (MTD). The highest dose (10 mg/kg) was administered to patients with advanced, recurrent SCLC (N=21) in phase II.
    
    Result:
    It was only possible to obtain pre-study biopsy samples for two patients, both of which showed cell surface GM2 overexpression of moderate intensity on immunohistochemistry testing. In phase I and II, all patients received the total planned dose. There were no dose-limiting toxicities in phase I and the MTD was not established. BIW-8982 10 mg/kg therefore used as the recommended phase II dose. The phase II study was prematurely terminated due to lack of efficacy. The objective response rate was 5.0% (95% CI, 0.1%–24.9%) in the efficacy evaluable population (N=20). Median overall survival was 304.0 days (95% CI, 70.0–406 days) and median progression free survival (PFS) was 43.0 days (95% CI, 38.0–43.0 days). One patient showed a durable partial response with PFS of 463 days and response duration of 382 days. There were a few patients with stable disease, which was generally not durable. No pattern of consistent toxicity was observed across the phases: there were no treatment-related adverse events (AEs) Grade ≥3, serious AEs, AEs leading to discontinuation of BIW-8962, or deaths. No unexpected trends or safety concerns were identified from laboratory parameter, vital sign, or electrocardiogram assessments. Anti-BIW-8962 antibodies were not detected in serum of any patient before or following treatment. Exploratory analysis of circulating tumor cells and other potentially predictive or pharmacodynamic markers did not reveal any results consistent with an effect from BIW-8962.
    
    Conclusion:
    This study was prematurely terminated due to lack of efficacy, for which the reason is unknown. Clinical development of BIW-8962 has been discontinued.