Author of

• 20039

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  Poster Display Session (ID 63)

  • Event: ELCC 2017
  • Type: Poster Display Session
  • Track:
  • Presentations: 2
  • Moderators:
  • Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1

  • 19899

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    143TiP - IMpower110: Phase III trial of 1L atezolizumab in PD-L1–selected chemotherapy-naive NSCLC (ID 364)

    12:30 - 13:00  |  Author(s): A. Lopez-Chavez
    • Abstract

    Background:
    Despite poor survival and toxicities, chemotherapy is the standard of care and remains the main first-line option for patients (pts) with advanced NSCLC non-squamous (non-sq) and squamous (sq) histology without genetic driver alterations. Immunotherapies targeting PD-L1/PD-1 are available for 2L+ NSCLC but remain to be fully studied in the 1L setting. Atezolizumab (atezo), an anti–PD-L1 mAb, prevents PD-L1 interacting with PD-1 and B7.1, restoring tumor-specific T-cell immunity. Significant and clinically relevant survival benefit has been shown with atezo in previously treated NSCLC, regardless of PD-L1 expression on tumor cells (TC) and/or tumor-infiltrating immune cells (IC). IMpower110 (NCT02409342), a global Phase III randomized, multicenter, open-label trial, will evaluate efficacy and safety of 1L atezo vs cisplatin (cis)/carboplatin (carbo) + pemetrexed (pem) or gemcitabine (gem) in PD-L1–selected chemotherapy-naive pts with advanced non-sq or sq NSCLC, respectively.
    
    Trial design:
    Inclusion criteria include stage IV non-sq or sq NSCLC, measurable disease (RECIST v1.1), ECOG PS 0-1, no prior chemotherapy for advanced NSCLC and centrally assessed PD-L1 expression of ≥ 1% on TC or IC (TC1/2/3 or IC1/2/3 with VENTANA SP142 IHC assay; expected prevalence, ≈ 65%). Exclusion criteria include active or untreated CNS metastases, prior immune checkpoint blockade therapy or autoimmune disease. Pts will be randomized 1:1 to receive atezo or cis/carbo + pem (non-sq)/gem (sq) (4 or 6 21-day cycles are allowed). Pts receiving atezo may continue until loss of clinical benefit, while pts in the comparator arm can receive pem maintenance (non-sq) or best supportive care (sq) until disease progression. Stratification factors are sex, ECOG PS, histology (non-sq vs sq) and centrally assessed PD-L1 expression by IHC. Co-primary endpoints are PFS and OS. Key secondary endpoints are ORR, DOR, IRF-assessed PFS (RECIST v1.1) and TTD in pt-reported lung cancer symptoms. Safety and PK will also be evaluated. Tumor biopsies at progression will be assessed for immunologic biomarkers associated with responses to atezo and to differentiate unusual responses from radiographic progression. Approximately 570 pts will be enrolled.
    
    Clinical trial identification:
    NCT02409342
    
    Legal entity responsible for the study:
    F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group
    
    Funding:
    F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group
    
    Disclosure:
    J. Jassem: Speaker: AstraZeneca, Roche, Pfizer; Advisory roles: AstraZeneca, Boehringer, BMS, Celgene, G1 Therapeutics, Merck, Pfizer, Pierre Fabre, Roche; Travel support: Roche, Boehringer. F. de Marinis: Consultation fees received from Roche/BMS/Boehringer/Novartis/Pfizer/MSD/Astrazeneca. D.R. Spigel: Consulting/Advisory Role: Genentech (uncompensated); Travel, accommodation, expenses: Genentech. S. Lam, S. Mocci, A. Sandler, A. Lopez-Chavez, Y. Deng: Employee, stock: Roche/Genentech. G. Giaccone: Consulting or Advisory Role: Clovis, Boehringer-Ingelheim; Celgene; Research grants: Karyopharm, Astra-Zeneca; Eli-Lilly. R.S. Herbst: Consultant and research support from Genentech
    
    

  • 19833

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    58TiP - IMpower133: Phase I/III trial of first-line atezolizumab with carboplatin and etoposide in ES-SCLC (ID 421)

    12:30 - 13:00  |  Author(s): A. Lopez-Chavez
    • Abstract

    Background:
    Platinum-based chemotherapy (chemo) with etoposide is the current first-line standard of care for the majority of patients (pts) with ES-SCLC. However, survival outcomes remain poor (median OS, < 1 year) despite initial response rates ranging from 50%-70%. Atezolizumab (atezo) is an anti–PD-L1 mAb that prevents the interaction of PD-L1 with its receptors, PD-1 and B7.1, and restores antitumor T-cell activity. Tolerable safety with promising durability of response has been shown with atezo in pts with ES-SCLC: confirmed ORR was 6% (n = 1/17 [partial response]; DOR of 7 mo) by RECIST v1.1 and 24% by immune-related response criteria (irRC; n = 4/17, with 2 pts on atezo for ≥ 12 mo). Preliminary data also indicate the potential synergy between atezo and platinum-based chemo in NSCLC whereby durable responses may translate into improved survival compared with atezo alone. IMpower133 (NCT02763579), a global, Phase I/III, randomized, multicenter, double-blinded, placebo-controlled trial, will evaluate the efficacy and safety of 1L atezo + carboplatin + etoposide compared with placebo + carboplatin + etoposide in treatment-naive pts with ES-SCLC.
    
    Trial design:
    Eligibility criteria include ES-SCLC, measurable disease (RECIST v1.1), ECOG PS 0-1 and no prior systemic anticancer treatment. Exclusion criteria include untreated CNS metastases and history of autoimmune disease. Submission of tumor tissue is a study requirement but pts will be enrolled regardless of biomarker status. Stratification factors are sex, ECOG performance status and presence of treated brain metastases. Eligible pts will be randomized 1:1 to receive four 21-day cycles of atezo (1200 mg IV) or placebo in combination with carboplatin (AUC 5 mg/mL/min IV, d 1) and etoposide (100 mg/m[2] IV, d 1-3), followed by maintenance therapy with atezo or placebo until PD per RECIST v1.1. Pts can continue with treatment until persistent radiographic PD, symptomatic deterioration or unacceptable toxicity. Co-primary endpoints are investigator-assessed PFS per RECIST v1.1 and OS. Secondary efficacy endpoints include investigator-assessed ORR and DOR. Safety and tolerability will also be assessed. Approximately 400 pts will be enrolled.
    
    Clinical trial identification:
    NCT02763579
    
    Legal entity responsible for the study:
    F. Hoffmann-La Roche Ltd/Genentech Inc.
    
    Funding:
    F. Hoffmann-La Roche Ltd/Genentech Inc.
    
    Disclosure:
    M. Reck: Honoraria for lectures and consultancy with Boehringer-Ingelheim, Hoffmann-La Roche, Lilly, MSD, BMS, AstraZeneca, Celgene, Merck, Pfizer. A.S. Mansfield: Advisory Board: Genentech, BMS, and Trovagene. S.V. Liu: Advisory board/consultant for: Genentech, Pfizer, Ariad, Celgene, Boehringer Ingelheim, Lilly. T.S.K. Mok: Grant/Speaker/AdBoards: AZ, BI, Pfizer, Novartis, SFJ, Roche, MSD, Clovis, BMS, Eisai, Taiho, Lilly, Merck, ACEA, Vertex, BMS, geneDecode, OncoGenex, Celgene, Ignyta, Taiho; Stock: Sanomics; Board: IASLC, CLCRF, CSCO, HKCTS. X. Tang: Roche employee. S. Lam: Roche/Genentech: employee, stock. F. Kabbinavar, A. Lopez-Chavez, A. Sandler: Employee, stock: Roche/Genentech. L. Horn: Advisory board: Genentech; Consulting: Abbvie, Merck, Lilly, Xcovery and EMD Serono.