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L. Xu

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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
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      195TiP - A phase 3, randomized, double-blind study of epacadostat plus pembrolizumab vs pembrolizumab as first-line therapy for metastatic non-small cell lung cancer (mNSCLC) expressing high PD-L1 levels (ECHO-305/KEYNOTE-654) (ID 414)

      12:30 - 13:00  |  Author(s): L. Xu

      • Abstract

      Epacadostat (E) is a potent, highly selective oral inhibitor of indoleamine 2,3 dioxygenase-1 (IDO1), a tryptophan-catabolizing enzyme that shifts the tumor microenvironment to an immunosuppressive state responsible for tumor escape from immune surveillance. Pembrolizumab (P), a PD-1 inhibitor, is the standard of care for treatment-naive patients with mNSCLC, high PD-L1 expression (tumor proportion score [TPS] ≥50%), and no EGFR or ALK genomic aberrations. Preliminary data from the phase 1/2 ECHO-202/KEYNOTE-037 study suggest that E + P is generally well tolerated and active in NSCLC regardless of PD-L1 expression. The ECHO-305/KEYNOTE-654 global study compares the efficacy and safety of first-line E + P vs P in patients with PD-L1 high mNSCLC.

      Trial design:
      Eligible patients are ≥18 years old with stage IV NSCLC for whom EGFR-, ALK-, or ROS1-directed therapy is not indicated, TPS ≥50%, ECOG PS 0 or 1, and no prior systemic therapy for mNSCLC. Patients who received prior IDO1 inhibitors or immune checkpoint therapies are excluded. Approximately 588 patients will be randomized 1:1 to E 100 mg oral BID + P 200 mg IV Q3W or P + E-matched placebo. Patients will be stratified by tumor histology (squamous vs nonsquamous), ECOG PS (0 vs 1), and geographical location (East Asia vs non-East Asia). Treatment will continue for up to 35 cycles of P or until disease progression, intolerable toxicity, or investigator or patient decision to withdraw. Treatment may continue beyond initial radiographic progression in eligible patients. Patients may discontinue treatment following confirmed complete response. The primary endpoints are PFS and OS. Secondary endpoints include ORR, duration of response, safety, tolerability, and E pharmacokinetics. Response will be assessed by RECIST v1.1 (blinded independent central review) every 9 weeks up to week 54 and every 12 weeks thereafter. 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:

      Legal entity responsible for the study:
      Incyte Corporation, Wilmington, DE, USA and Merck & Co., Inc., Kenilworth, NJ, USA

      Incyte Corporation, Wilmington, DE, USA and Merck & Co., Inc., Kenilworth, NJ, USA

      L. Paz-Ares: Honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, MSD, Pfizer, Roche, Merck and Novartis. S. Rubin, Y. Zhao: Employee and stockholder of Incyte. L. Xu, A. Samkari: Employee and stockholder of Merck. M. Awad: Consulting or advisory role for Abbvie, ARIAD, AstraZeneca/MedImmune, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, Foundation Medicine, Genentech, Merck, Nektar, and Pfizer.