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H. Borghaei



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    Immunotherapies and targeted therapies in advanced NSCLC (ID 39)

    • Event: ELCC 2017
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
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      83O - A phase II study of durvalumab (MEDI4736) for previously treated patients with stage IV squamous NSCLC (SqNSCLC): Lung-MAP Sub-study SWOG S1400A (ID 279)

      14:45 - 16:15  |  Author(s): H. Borghaei

      • Abstract
      • Presentation
      • Slides

      Background:
      Durvalumab (MEDI4736) is an engineered human IgG1 mAb targeting programmed cell death ligand-1 (PD-L1). Treatment with other anti-PD-1/PD-L1 antibodies has demonstrated meaningful clinical benefit in patients with advanced NSCLC.

      Methods:
      As part of the Lung Master Protocol S1400, a National Clinical Trials Network group "umbrella" trial for second-line SqNSCLC we conducted a phase II study of durvalumab in patients with Stage IV squamous NSCLC (ECOG PS 0-2; ≥1 prior systemic treatment regimens, including one platinum-based), EGFR/ALK wild-type. The primary endpoint was overall response rate (ORR) (RECIST v1.1); secondary endpoints included duration of response (DoR), ORR among PD-L1 positive patients, disease control rate (DCR), investigator-assessed progression-free survival (PFS), overall survival (OS) and safety (CTCAE v4.03). The initial protocol was a randomized phase II/III comparison of durvalumab to docetaxel, and was amended to be a single arm phase II trial of single agent durvalumab. PD-L1 positive tumors were defined by ≥ 25% of tumor cells with membrane staining.

      Results:
      Of the 68 eligible patients (median [range] age 66 [35-92] years, PS 0/1/2 26%/62%/12%), 11 were responders (16% ORR, 95% Confidence Interval [CI] 7%, 25%). DCR was 54% (CI 43%, 66%), median OS was 11.5 months (CI 10.1-12.4 mos), and median PFS was 2.9 mos (CI 2.0-4.1 mos). Of the 11 responders, median time to response and DoR were 3.6 mos (CI 2.8-4.2 mos) and 18.6 months (95% CI 4.4-NR mos), respectively. Of the 14 PDL1-positive patients, 2 were responders (14% ORR, 95% CI 0%, 33%), DCR was 57% (CI 31%, 83%), median OS and PFS were 10.7 mos (CI 9.2-10.7 mos) and 2.3 mos (CI 1.4-4.9 mos), respectively. Durvalumab showed a manageable safety and tolerability profile; most adverse events (AEs) were low grade and resolved with treatment delay and/or immunosuppressive interventions. Grade ≥3 treatment-related AEs occurred in 23(34%) of patients. Drug-related AEs led to discontinuation in 6 patients (9%, 95% CI 2%, 16%).

      Conclusions:
      Durvalumab demonstrated clinical benefit and durable responses in a previously treated metastatic NSCLC population with manageable toxicity profile. Results are comparable with other anti-PD-1/PD-L1 therapies in metastatic, relapsed NSCLC.

      Clinical trial identification:
      NCT02766335

      Legal entity responsible for the study:
      Southwest Oncology Group/NCTN

      Funding:
      Lung-MAP supported in part by NIH/NCI grants CA180888, CA180819, CA180820, CA180821, CA180868, and by Amgen, AstraZeneca, Bristol-Myers Squibb Company Genentech and Pfizer through the Foundation for the National Institutes of Health, in partnership with Friends of Cancer Research.

      Disclosure:
      V. Papadimitrakopoulou: Advisory Role for: Eli Lilly&Co, Genentech, Janssen Global Sevices, Bristol-Myers Squibb, ARIAD, Astra Zeneca Pharmaceuticals, Novartis, Merck Corporate-sponsored research: Novartis, Astra Zeneca, Genentech, Merck, Janssen, ACEA, Bristol-Myers Squibb. H. Borghaei: Advisory: Bristol-Myers Squibb, Lilly, Genentech, Celgene, Pfizer, EMD-Serono, Boerhinger-Ingelheim, Trovagene, AstraZeneca, Research Support: Millenium, Merck, Celgene. K. Kelly: Advisory: Synta, AstraZeneca, Lilly, Clovis Oncology, ARIAD, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, G1 Therapeutics. Research: Millenium, Novartis, EMD Serono, Lilly, Genentech, Abbvie, Gilead, Celgene, Five Prime Therapeutics, Transgene. All other authors have declared no conflicts of interest.

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    Poster Display Session (ID 63)

    • Event: ELCC 2017
    • Type: Poster Display Session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1
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      144TiP - CheckMate 227: A randomized, open-label phase 3 trial of nivolumab, nivolumab plus ipilimumab, or nivolumab plus chemotherapy versus chemotherapy in chemotherapy-naïve patients with advanced non-small cell lung cancer (NSCLC) (ID 394)

      12:30 - 13:00  |  Author(s): H. Borghaei

      • Abstract

      Background:
      Platinum-based chemotherapy is standard-of-care first-line therapy for most patients with advanced NSCLC, but the clinical benefit is modest. Although first-line nivolumab, an immune checkpoint inhibitor antibody, did not improve progression-free survival or overall survival (OS) versus chemotherapy in patients with advanced NSCLC and ≥5% programmed death-1 ligand 1 (PD-L1) expression, OS compared favorably with historical controls of first-line platinum-based chemotherapy. Combining nivolumab with chemotherapy in this setting may increase the durability of tumor responses and broaden the population of patients to derive benefit. In a multi-cohort phase 1 study (CheckMate 012) in chemotherapy-naïve patients with advanced NSCLC, nivolumab plus chemotherapy had promising clinical activity, regardless of tumor PD-L1 expression, and a manageable safety profile. CheckMate 227 is a 2-part, randomized, open-label phase 3 trial (NCT02477826), evaluating first-line nivolumab, nivolumab plus ipilimumab, or nivolumab plus chemotherapy versus chemotherapy in patients with advanced NSCLC.

      Trial design:
      Part 1 of CheckMate 227, which has completed accrual, enrolled adult patients with stage IV/recurrent NSCLC, no prior systemic anticancer therapy, and assessment of PD-L1 expression at screening. Patients with ≥1% PD-L1 expression were randomized 1:1:1 to nivolumab, nivolumab plus ipilimumab, or chemotherapy arms; those with <1% PD-L1 expression were randomized 1:1:1 to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy arms. In part 2, ∼480 previously untreated patients with advanced NSCLC, regardless of PD-L1 expression level, will be randomized 1:1 to receive histology-based platinum doublet chemotherapy alone or in combination with nivolumab. Part 2 of CheckMate 227, which is the focus of this presentation, allows for the evaluation of first-line nivolumab plus chemotherapy in a broad group of patients with advanced NSCLC across the PD-L1–expressing continuum.

      Clinical trial identification:
      NCT02477826

      Legal entity responsible for the study:
      Bristol-Myers Squibb

      Funding:
      Bristol-Myers Squibb

      Disclosure:
      L. Paz-Ares: Served as a medical advisor for the following companies: Lilly, Roche, MSD, BMS, Celgene, Pfizer, Boehringer-Ingelheim, Bayer, Clovis, and AstraZeneca. J. Brahmer: Received research grants and served as an uncompensated advisory board member for Bristol-Myers Squibb. M.D. Hellmann: Received grants from Genentech and Bristol-Myers Squibb. Received personal fees from Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, Novartis, and Janssen. M. Reck: Received consultant fees and served on speaker\'s bureau for the following companies: Roche, Lilly, Bristol-Myers Squibb, MSD, AstraZeneca, Pfizer, Boehringer-Ingelheim, and Celgene. K. O\'Byrne: Received honoraria, speaker bureau and/or travel and registration support for national and international meetings from BMS, Boehringer-Ingelheim, Astrazeneca, Lilly Oncology, Novartis, MSD, Roche-Genentech and Pfizer. H. Borghaei: The institution has a clinical trial agreement w/BMS. Consultant/advisory board member for: BMS, Lilly, Genentech, Celgene, EMD-Serono, Merck, Pfizer, Trovagene, Millenium, & Boehringer-Ingelheim. Received grants from: Millenium, Merck, & Celgene. W.J. Geese, H. Lu: BMS Employee and stock holder. F.E. Nathan: BMS employee. S. Ramalingam: Served on ad hoc scientific advisory board meetings the following companies: Astra Zeneca, BMS, Boehringer Ingelheim, Celgene, Ariad, Amgen, Lilly, Merck, Genentech. Also received honoraria from BMS.