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Y. Zhao



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    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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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. Zhao

      • 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.

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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): Y. Zhao

      • Abstract

      Background:
      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:
      NCT03322540

      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:
      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.