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G.J. Kiefer



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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): G.J. Kiefer

      • 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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