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L. Zhang

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    MA16 - Novel Strategies in Targeted Therapy (ID 407)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Chemotherapy/Targeted Therapy/Immunotherapy
    • Presentations: 1
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      MA16.06 - Phase I/II Study of AC0010, Mutant-Selective EGFR Inhibitor, in Non-Small Cell Lung Cancer (NSCLC) Patients with EGFR T790M Mutation (ID 5117)

      14:20 - 15:50  |  Author(s): L. Zhang

      • Abstract
      • Presentation
      • Slides

      AC0010 was designed specifically to inhibit EGFR active mutations and the T790M acquired resistant mutation. The purpose of the study is to determine the safety, antitumor activity and recommended phase II dose of AC0010 in T790M-postitive NSCLC patients after the first generation EGFR TKIs treatment.

      This is a dose escalation and expansion phase I/II study. Oral AC0010 was administered on a 28-day cycle with the starting dose at 50 mg BID. In any given dose cohort, if 1 out of 3 patients was evaluated as PR at the first cycle, and no DLT determined, up to 20 patients will be enrolled. Plasma samples were collected to evaluate pharmacokinetics of AC0010. T790M in biopsy samples was detected by a central laboratory. NCT02330367.

      As of 10 Jul 2016, 136 patients have been treated across 7 cohorts (50, 100, 150, 200, 250, 300, and 350 mg BID). At the 30 Jun 2016 cutoff, 124 pts were evaluable. MTD has not been reached. The most common adverse events (AE) regardless of study drug relationship were diarrhea (38%), rash (26%) and ALT/AST elevation. Most AEs were grade 1 and 2. The most common Grade 3/4 drug-related AE was diarrhea (2%) rash (2%) and ALT/AST elevation (4%, 2%). All patients with AEs of the grade 3/4 were recovered after either stopped the treatment or reduced the dose. As of the cutoff date, there is no Grade 2,3 hyperglycemia, and grade 3 QTc prolongation. RECIST responses were observed at all dose levels except 50 mg BID. Amongst 124 evaluable patients in all cohorts, ORR (including unconfirmed responses) and disease control rate (DCR) was 44% and 85% respectively. In the dose cohorts between 150 mg BID and 300 mg BID (n=95 pts), the ORR and DCR were 51% and 89%. PK shows rapid absorption with a T~max~ of 2-4h and a median T1/2 of 8 h. At 300 mg BID, total 32 patients were treated and ORR and DCR are 53% and 90% respectively. Based on the efficacy, safety and PK results, the 300 mg BID was selected as RP2D. The phase II, AEGIS-1 study has started.The Phase II result will be presented.

      AC0010 shows a safe profile and antitumor activity against T790M mt NSCLC. Phase II, AEGIS-1 study is ongoing to evaluate therapeutic outcomes as a second line treatment for T790M positive NSCLC patients. Clinical trial information: NCT02330367

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