Author of

• 25520

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  Poster Display session (Friday) (ID 65)

  • Event: ELCC 2018
  • Type: Poster Display session
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1

  • 25393

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    193TiP - Phase 3 study of epacadostat plus pembrolizumab with or without platinum-based chemotherapy vs pembrolizumab plus chemotherapy for first-line metastatic non-small cell lung cancer (mNSCLC): ECHO-306/KEYNOTE-715 (ID 415)

    12:30 - 13:00  |  Author(s): Y. Luo
    • Abstract

    Background:
    Combination therapies targeting broad immunosuppression in the tumor microenvironment (TME) may prolong survival. Upregulation of the indoleamine 2,3 dioxygenase-1 (IDO1) enzyme within TME contributes to an immunosuppressive state responsible for tumor escape from immune surveillance. Epacadostat (E), a potent and selective inhibitor of IDO1, is under investigation in several tumor types. Pembrolizumab (P) is FDA-approved for NSCLC. In a phase 1/2 study, E + P showed minimal additive toxicity vs monotherapy and encouraging efficacy in NSCLC. The ECHO-306/KEYNOTE-715 global study compares the efficacy and safety of first-line E + P±chemotherapy vs P + chemotherapy in patients with mNSCLC.
    
    Trial design:
    Eligible patients: age ≥18, stage IV NSCLC (no EGFR-sensitizing mutation and ROS1/ALK translocations), ECOG PS ≤1, no prior systemic therapy for mNSCLC, and no prior IDO1 inhibitors or immune checkpoint therapies. Patients (∼1062) will be randomized 1:1:1 (E 100 mg oral BID + P 200 mg IV Q3W±platinum-based chemotherapy [nonsquamous: pemetrexed 500 mg/m[2] + cisplatin 75 mg/m[2] or carboplatin AUC 5 Q3W for 4 cycles followed by pemetrexed 500 mg/m[2] Q3W; squamous: paclitaxel 175–200 mg/m[2] + carboplatin AUC 5–6 Q3W for 4 cycles]; or E-matched placebo + P + chemotherapy) and stratified by tumor histology (squamous vs nonsquamous), PD-L1 status (tumor proportion score <50% vs ≥50%), ECOG PS (0 vs 1), and region (East Asia vs non-East Asia). Patients will receive treatment for ≤35 cycles of P or until disease progression (PD), intolerable toxicity, or investigator/patient decision to withdraw. Treatment may continue after initial radiographic PD in eligible patients. Patients may discontinue treatment after confirmed complete response. Primary endpoints: OS and PFS. Secondary endpoints: ORR per RECIST v1.1 (blinded central review; weeks 6, 12, 18, Q9W up to week 54 and Q12W thereafter), safety and tolerability, and E pharmacokinetics. Adverse events (AEs) will be monitored throughout the study and for 30 days (90 days for serious AEs) after end of treatment and graded per CTCAE v4.0.
    
    Clinical trial identification:
    NCT03322566
    
    Legal entity responsible for the study:
    Incyte Corporation, Wilmington, DE, USA and Merck & Co., Inc., Kenilworth, NJ, USA
    
    Funding:
    Incyte Corporation, Wilmington, DE, USA and Merck & Co., Inc., Kenilworth, NJ, USA
    
    Disclosure:
    M. Garassino: Received research funding from AstraZeneca (Inst), Bristol-Myers Squibb (Inst), Lilly (Inst), Merck Sharp & Dohme (Inst), and Roche (Inst), and received travel/accommodations/expenses from AstraZeneca, Bristol-Myers Squibb, and Roche. S. Rubin, Y. Zhao: Employee and stockholder of Incyte. Y. Luo, A. Samkari: Employee and stockholder of Merck. R. Hui: Advisory board member for Merck Sharp and Dohme, AstraZeneca, Novartis, Roche, and Bristol-Myers Squibb. Received speaker honorarium from Merck Sharp and Dohme.