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K.J. Lim



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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
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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): K.J. Lim

      • 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.

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    P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.11-010 - Phase I study of HM61713, a novel epidermal growth factor receptor (EGFR) mutant selective inhibitor, in non-small cell lung cancer (NSCLC) patients having an activating EGFR mutation but failed to prior EGFR tyrosine kinase inhibitor (TKI) therapy. (ID 1048)

      09:30 - 09:30  |  Author(s): K.J. Lim

      • Abstract

      Background
      NSCLC patients having an activating EGFR mutation initially responded well to EGFR TKI but most of them experienced progressive disease due to various resistance mechanisms including T790M (~50% of cases) mutation. HM61713 is an orally active, novel EGFR mutant selective inhibitor showing a strong anticancer activity in many lung cancer cell lines including T790M mutation harboring cell line. Therefore, HM61713 might provide the potential clinical benefit to those who have an activating EGFR mutation but have failed previous EGFR TKI treatment.

      Methods
      This is a phase I study using a standard 3+3 dose escalation scheme. NSCLC Patients with activating EGFR mutation and progressed after at least 2 prior chemotherapy regimens including EGFR TKI were eligible. The objective of this study is to determine the recommended phase II dose as well as to assess the preliminarily efficacy.

      Results
      To date, a total of 23 patients were treated with at doses of 75-250 mg/day. One patient at a dose of 200 mg/day experienced grade 3 drug induced idiosyncrasy and grade 4 elevation of amylase. The drug induced idiosyncrasy was skin rash of non-EGFR TKI type. The most common drug-related adverse events were desquamation, diarrhea, pruritus, and nausea; most were grade 1 or 2. The maximum tolerated dose (MTD) and recommended phase II dose were not determined yet. Plasma concentration of HM61713 reached the peak 2-4 hr after administration and declined with the half-life of 8-12 hr. Among 21 evaluable patients, 2 patients achieved partial response (PR) and one of them had confirmed T790M mutation while 12 patients had stable disease (SD) including 11 patients showed tumor shrinkage. Accrual to this study is ongoing and updated data will be presented at the meeting.

      Conclusion
      HM61713 showed good safety profile and promising anticancer activity in NSCLC patients with EGFR mutation who failed to prior EGFR TKI therapy. These results support the therapeutic potential of HM61713 for NSCLC patients with activating EGFR mutations after development of resistance to EGFR TKI therapy.