Author of

• 10801

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  P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10828

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    P1.11-027 - Phase I studies of HM781-36B, an irreversible pan-HER tyrosine kinase inhibitor (TKI) in patients with advanced solid tumor and the therapeutic potential in patients with advanced non-small cell lung cancer (NSCLC) (ID 2029)

    09:30 - 09:30  |  Author(s): T.M. Kim
    • Abstract

    Background
    HM781-36B is an irreversible pan-HER TKI, which showed a strong anticancer activity in many cell lines, including epidermal growth factor receptor (EGFR) TKI resistant ones in preclinical studies. Two phase I studies were conducted to determine the maximum tolerated dose (MTD) in patients with advanced solid tumor.

    Methods
    Patients with advanced malignancies refractory to standard therapies were eligible. Standard 3+3 dose escalation scheme was used in two phase I studies; a 2-weeks on / 1-week off schedule and a continuous dosing schedule.

    Results
    A total of 75 patients were enrolled; 55 patients in the 2-weeks on / 1-week off schedule and 20 patients in the continuous dosing schedule. 27 NSCLC patients were enrolled. Among 25 evaluable NSCLC patients, 3 patients achieved partial response (PR) and 10 patients had stable disease (SD). All 3 patients who achieved PR were previously treated with gefitinib, and one of them harbored EGFR T790M mutation. In addition, two of them had been treated with 4 or more regimens. Among 10 SD patients, 5 patients showed some degree of tumor shrinkage. Dose -limiting toxicity (DLT) was grade 3 diarrhea. The MTD was determined as 24 mg/day in the 2-weeks on / 1-week off schedule and 18 mg/day in the continuous dosing schedule. The recommended phase II dose was 16 mg/day (continuous) on the basis of toxicity, pharmacokinetic and pharmacodynamic profiles. Two phase II studies of HM781-36B are ongoing in NSCLC patients with previously EGFR TKI treated and EGFR TKI naive, respectively.

    Conclusion
    HM781-36B showed good safety profile and anticancer activity in NSCLC patients in two phase I studies. Effectiveness in the gefitinib refractory and heavily pretreated patients supported the potential of HM781-36B as a therapeutic agent for NSCLC.