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)

  • 17574

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    P2.03a-018 - A Phase I/II Study of Alisertib, an Oral Aurora Kinase Inhibitor, in Combination with Erlotinib in Patients with Recurrent or Metastatic NSCLC (ID 5197)

    14:30 - 14:30  |  Author(s): S. Litwin
    • Abstract

    Background:
    Erlotinib (E) is an oral reversible tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR), known to have efficacy in NSCLC. The aurora kinases are necessary for cell cycle regulation and may have altered function in certain cancers; alisertib (A) is an oral selective aurora kinase A inhibitor. Preclinical data suggested that the combination of an EGFR inhibitor and aurora kinase inhibitor may have synergistic effects in wild-type EGFR NSCLC patients, leading to this phase I/II trial.
    
    Methods:
    Using a 3 + 3 dose escalation design, A was increased over four dose levels from 30 mg - 50 mg twice daily. E was given daily at 100 mg in DL1 and 150 mg in DL2-4. A was given on days 1-7 of a 21 day cycle along with daily E. Key eligibility criteria: age > 18, histologically confirmed NSCLC, ECOG PS 0-1, prior appropriate first line therapy, acceptable organ function. Key exclusion criteria: EGFR mutation, prior treatment with an EGFR pathway inhibitor or aurora kinase inhibitor.
    
    Results:
    We report our experience with the phase I portion of this study and plans for the phase II portion. Eighteen patients were treated on four dose levels. Patient characteristics: Median age 61, M/F (8/10), 10/18 had received RT in addition to systemic therapy. 14/18 patients completed at least 2 cycles. Median number of cycles completed was 4.6. Common drug-related AEs of any grade were fatigue (89%), anemia (83%), leukopenia (78%), dyspnea (78%), diarrhea and anorexia (61% respectively). Drug-related Grade 3/4 AE included neutropenia and leukopenia (33% each), febrile neutropenia, lymphopenia and anemia (11% each). Two DLT occurred at DL4 (febrile neutropenia, neutropenia delaying a cycle by > 7 days, both in cycle 1). Disease responses were noted, including one patient with a PR who completed 10 cycles, and 5 patients who achieved SD.
    
    Conclusion:
    In patients with recurrent/metastatic NSCLC, the combination of A and E was tolerable. However, the maximum administered dose (E 150 mg daily + E 50 mg BID) led to two DLT, thus the MTD was declared at DL3 (E 150 mg + A 40 mg BID); anti-tumor activity was noted. Updated preclinical data from KRAS mutated and WT cell lines indicate activity of this combination in KRAS mutants whereas either drug alone is ineffective. Based on this data, a protocol amendment was submitted to allow only patients with KRAS mutations to be treated in the phase II portion of the study.