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A. Wozniak



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    P2.06 - Poster Session with Presenters Present (ID 467)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
    • Presentations: 1
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      P2.06-019 - A Phase II Study of Atezolizumab as Neoadjuvant and Adjuvant Therapy in Patients (pts) with Resectable Non-Small Cell Lung Cancer (NSCLC) (ID 4642)

      14:30 - 14:30  |  Author(s): A. Wozniak

      • Abstract

      Background:
      There is no curative treatment for patients with NSCLC who develop metastatic disease after resection. Trials of neoadjuvant and adjuvant chemotherapy have demonstrated an absolute survival benefit of 5% for patients with stages IB, II, and IIIA disease. Clearly, developing new treatment strategies to improve survival following resection is critical to improving outcomes for this patient population. Immunotherapy with checkpoint inhibitors such as antibodies to PD-1 and PD-L1 has demonstrated superior survival compared to chemotherapy in randomized clinical trials. PD-L1 expression is being investigated as a predictive biomarker for these therapies, but its ability to predict response has varied in published trials. Atezolizumab is a humanized IgG1 monoclonal PD-L1 antibody that was recently evaluated in the POPLAR trial (NCT01903993), a phase II randomized trial of patients with NSCLC who progressed on platinum based chemotherapy. Atezolizumab therapy improved overall survival compared with docetaxel (12.6 months vs. 9.7 months, HR 0.73 [95% CI 0.53 – 0.99]) with a manageable safety profile. Improvement in survival correlated with PD-L1 immunohistochemistry expression of tumor and tumor-infiltrating immune cells.

      Methods:
      Trial design: This phase II, open-label, single-arm study is designed to evaluate the efficacy and safety of atezolizumab as a neoadjuvant therapy in patients with Stage IB, II, or IIIA NSCLC prior to curative-intent resection. Approximately 180 patients with NSCLC will be enrolled in this study at 15 academic medical centers in the United States. There are two parts to this study: the first/primary part will evaluate the ability of neoadjuvant atezolizumab to produce objective pathologic responses in patients with early stage NSCLC. Atezolizumab 1200 mg IV will be given every 3 weeks for two doses. Surgical resection of tumors following treatment will allow determination of pathologic response rates and potential predictive biomarkers. Part 2 is exploratory and will evaluate atezolizumab adjuvant therapy for up to 12 months in patients who demonstrate clinical benefit (evidence of pathologic response or absence of radiographic progression) in Part 1. After surgical resection, patients may receive SOC adjuvant chemotherapy (with or without radiation) before starting atezolizumab adjuvant therapy in Part 2. The primary objectives are safety and major pathologic response based on surgical resection. Secondary objectives include overall response rate based on PD-L1 status, mutational load, antigen burden, and RNA-sequencing. This trial presents a unique opportunity to evaluate exploratory biomarkers, including pre- and post-treatment biopsy assessment of evolution of immune related markers associated with response.

      Results:
      Section not applicable

      Conclusion:
      Section not applicable

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    P3.02b - Poster Session with Presenters Present (ID 494)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.02b-115 - Clinical Activity of Osimertinib in EGFR Mutation Positive Non Small Cell Lung Cancer (NSCLC) Patients (Pts) Previously Treated with Rociletinib (ID 4893)

      14:30 - 14:30  |  Author(s): A. Wozniak

      • Abstract

      Background:
      Both osimertinib and rociletinib were developed to target the EGFR resistance mutation T790M. Sequist, et al reported clinical activity with osimertinib in 9 pts previously treated with rociletinib[1]. We conducted a retrospective analysis at 8 institutions of pts treated with rociletinib, who discontinued the drug due to disease progression or intolerable toxicity and subsequently received osimertinib.

      Methods:
      We identified pts treated with rociletinib followed by osimertinib, as part of osimertinib's US expanded access program or via commercial supply. Clinical characteristics and outcomes were assessed. Frequency of clinical and radiologic assessments on osimertinib was at the discretion of the treating physician. For this retrospective review, reverse KM method was used to calculate the median follow-up; KM method was used for time-to-event endpoints.

      Results:
      45 pts were included in this analysis. Median age at the start of osimertinib was 66 years (43-86) and 71% were female. 28 pts had exon 19 deletions and 16 had L858R. Median duration of therapy on front line EGFR TKI was 18 months (5-54). Median starting dose of rociletinib was 625 mg bid (range 500-1000). The response rate (RR) and disease control rate (DCR; Response+Stable Disease) with rociletinib were 38% and 91%; median duration of rociletinib therapy was 6.2 months. 32 (71%) pts discontinued rociletinib for disease progression. 23 (51%) pts received other therapies (1-4) before starting osimertinib. 25 (56%) pts were known to have brain metastases at osimertinib initiation. RR and DCR with osimertinib were 33% and 82%. DCR in the brain was 88%. With a median follow-up of 7.1 months, median duration of osimertinib therapy in all patients was 8 months (95%CI- 6.6-NR; 64% censored). The 1-year overall survival (OS) rate on osimertinib was 70% (54%-91%). In the 32 pts who discontinued rociletinib due to progression, DCR with osimertinib was 75% and median duration of therapy was 7.8 months (4.6-NR). Neither duration of,or response to rociletinib treatment, nor interval between the two the drugs was associated with duration of osimertinib or OS after osimertinib using a Cox model adjusted for age and sex.

      Conclusion:
      Osimertinib can provide clinical benefit in EGFR mutation positive NSCLC patients previously treated with rociletinib. The clinical activity of osimertinib in these patients may be related to more potent inhibition of T790M mutation or ability to overcome resistance to rociletinib. Reference- 1. Sequist, et al. JAMA Oncology 2016