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C. Zielinski

Moderator of

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    ISS01 - Industry Supported Symposium: Current and Emerging Treatments for Patients with ALK+ NSCLC – ARIAD Pharmaceuticals Inc. (ID 435)

    • Event: WCLC 2016
    • Type: Industry Supported Symposium
    • Track:
    • Presentations: 5
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      ISS01.01 - Welcome & Introduction (ID 7135)

      C. Zielinski, D..R. Camidge

      • Abstract

      Abstract not provided

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      ISS01.02 - ALK Inhibitors: Current Treatments and Sequencing (ID 7136)

      C. Zielinski

      • Abstract

      Abstract not provided

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      ISS01.03 - The Future of ALK Inhibitors: How the Treatment Paradigm May Change (ID 7137)

      D..R. Camidge

      • Abstract

      Abstract not provided

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      ISS01.04 - Will Mutation Testing be Standard in the Resistant Setting? (ID 7138)

      P. Jänne

      • Abstract

      Abstract not provided

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      ISS01.05 - Summary and Conclusions (ID 7139)

      C. Zielinski, D..R. Camidge

      • Abstract

      Abstract not provided

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    PR04 - Press Conference: Advanced Care (ID 404)

    • Event: WCLC 2016
    • Type: Press Conference
    • Track:
    • Presentations: 5
    • Now Available
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      PR04.01 - Health-Related Quality of Life for Pembrolizumab vs Chemotherapy in Advanced NSCLC with PD-L1 TPS ≥50%: Data from KEYNOTE-024 (Now Available) (ID 7213)

      J.R. Brahmer

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      PR04.02 - OAK, a Randomized Ph III Study of Atezolizumab vs Docetaxel in Patients with Advanced NSCLC: Results from Subgroup Analyses (Now Available) (ID 7214)

      S.M. Gadgeel

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      PR04.03 - Durvalumab in ≥3rd-Line Locally Advanced or Metastatic, EGFR/ALK Wild-Type NSCLC: Results from the Phase 2 ATLANTIC Study (Now Available) (ID 7215)

      M.C. Garassino

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      PR04.04 - Multicentric French Harmonization Study for PD-L1 IHC Testing in NSCLC (Now Available) (ID 7216)

      J. Adam

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      PR04.05 - A Phase II Study of Nivolumab in Malignant Pleural Mesothelioma (NivoMes): With Translational Research (TR) Biopies (Now Available) (ID 7217)

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    SC14 - Immunotherapy of NSCLC (ID 338)

    • Event: WCLC 2016
    • Type: Science Session
    • Track: Chemotherapy/Targeted Therapy/Immunotherapy
    • Presentations: 5
    • Now Available
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      SC14.01 - Immunotherapy in the First-Line Setting of Advanced NSCLC (Now Available) (ID 6653)

      R.S. Herbst

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Immunotherapy in the First-Line Setting of Advanced NSCLC Lung cancer remains the leading cause of cancer-related deaths worldwide. Advances in screening, surgery and treatment have helped to improve the median survival for patients with lung cancer over the past decade, however, the five-year survival rate remains less than 20%. The majority of patients are diagnosed with advanced stage disease, who are treated with platinum-based chemotherapy, followed by targeted, combination, or immunotherapies. Given the response rates seen with the use of immunotherapy in the second-line setting, it was appropriate to begin to explore if these agents could be given to patients earlier in their treatment. Immunotherapies have been found to be better tolerated than chemotherapy and have the potential for long-term survival, thus could benefit patients as first-line therapy, as some patients will never go on to receive second-line treatment. Two agents, nivolumab and pembrolizumab, both monoclonal antibodies targeting programmed cell death protein 1 (PD-1), are approved for use in patients with non-small cell lung cancer (NSCLC) who have received prior chemotherapy. The KEYNOTE-024 randomized phase III trial of pembrolizumab vs. standard of care (platinum-based chemotherapy), demonstrated superior progression-free survival (PFS) and overall survival (OS) for first-line treatment in patients with tumors expressing high levels of programmed cell death ligand 1 (PD-L1) (tumor proportion score ≥50%). The CheckMate-026 randomized, phase III study of nivolumab vs. standard of care in treatment-naïve patients with tumors expressing ≥5% PD-L1 did not meet the primary endpoint of PFS. For this presentation, the use of predictive markers in the front-line setting will be discussed and implications for combination therapy will be reviewed.

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      SC14.02 - Immunotherapy in the Second-Line Setting of Advanced NSCLC (Now Available) (ID 6654)

      L. Paz-Ares

      • Abstract
      • Presentation
      • Slides

      Abstract:


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      SC14.03 - Combination Immunotherapy - Basic Considerations and First Outcomes (Now Available) (ID 6655)

      D. Spigel

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      SC14.04 - The CD47 Macrophage Checkpoint as a New Immunotherapy Target (Now Available) (ID 6656)

      B. Sikic, S.K. Padda, S.A. Shah, A..D. Colevas, S. Narayanen, G. Fisher, D. Supan, H. Wakelee, R. Aoki, M.D. Pegram, V.M. Villalobos, J. Liu, C. Takimoto, M.P. Chao, J.P. Volkmer, R. Majeti

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Background: Hu5F9-G4 is a humanized monoclonal antibody that targets CD47, blocking its anti-phagocytic “don’t eat me” signal through macrophage receptor SIRPα, leading to tumor phagocytosis. CD47 is overexpressed on human cancers and also on red blood cells (RBCs). In primate toxicology studies, Hu5F9-G4 caused a transient anemia that was improved with a single lower Priming Dose allowing higher Maintenance Doses. Materials and Methods: Relapsed/refractory solid tumors and lymphomas were included. This dose escalation study included: Part A, to determine the Priming Dose and Part B, to determine the Maintenance Dose. The maximum tolerated dose (MTD) in part A was used for the single Priming Dose in part B (Hu5F9-G4 dosed weekly). The primary objective is to determine safety and secondary objectives are to determine PK and PD. Preliminary data reported from data cutoff of July 22, 2016.Results: 25 patients have enrolled. Part A included 0.1 (N=1), 0.3 (N=2), 1 (N=6), and 3 (N=2) mg/kg. There were 2 dose-limiting toxicities (DLTs) in Part A at the 3 mg/kg dose: grade (G) 3 abdominal pain and G3 hemagglutination (H) (protocol-specific scale of G1 H on peripheral blood smear (PBS) and G2 headache). 1 mg/kg was selected as the Priming Dose, with no >G2 anemia. Pharmacodynamic studies show almost 100% RBC receptor occupancy at the Priming Dose. Treatment-related adverse event (TRAE) in Part A included: anemia (3 G1, 3 G2), hyperbilirubinemia (3 G1, 2 G2; unconjugated), headache (6 G1, 1 G2), H on PBS (8 G1), and nausea (3 G1). Part B included 3 (N = 4), 10 (N = 3), and 20 mg/kg (N=6, ongoing). There have been no DLTs in 3 patients on 10 mg/kg, and one DLT (headache with hemagglutination) in 6 patients at the 20 mg/kg maintenance dose (ongoing). Most toxicities were was associated with the initial single Priming Dose and were completely reversible. TRAE in Part B at 3 mg/kg included: anemia (2 G1, 2 G2), hyperbilirubinemia (1 G1, 1 G3), headache (3 G1), H on PBS (1 G1), retinal toxicity (G2 protocol-specific scale, asymptomatic). TRAE at 10 mg/kg included: anemia (3 G1), headache (2 G1), and nausea (1 G1). Two patients with adenoid cystic carcinoma in Part A had stable disease for 16 and 8 months. In Part B, 2 of 3 patients have had prolonged stable disease at 10 mg/kg for 8+ months (follicular thyroid cancer) and 7+ months (myoepithelioma of the head and neck). Evaluation of subjects in the 20 mg/kg cohort is ongoing. Conclusions: Hu5F9-G4 is well tolerated at 10 mg/kg weekly, with 1 mg/kg Priming Dose. Part B with a Maintenance Dose of 20 mg/kg is ongoing. Acknowledgements: Stanford Clinical and Translational Research Unit; California Institute for Regenerative Medicine; Forty Seven, Inc.Trial Registration: NCT02216409References: 1. Willingham SB, et al. The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6662-7. 2. Liu J t al. Pre-Clinical Development of a Humanized Anti-CD47 Antibody with Anti-Cancer Therapeutic Potential. PLoS One. 2015 Sep 21;10(9):e0137345. References 1. Willingham SB, Volkmer JP, Gentles AJ, Sahoo D, Dalerba P, Mitra SS, Wang J, Contreras-Trujillo H, Martin R, Cohen JD, Lovelace P, Scheeren FA, Chao MP, Weiskopf K, Tang C, Volkmer AK, Naik TJ, Storm TA, Mosley AR, Edris B, Schmid SM, Sun CK, Chua MS, Murillo O, Rajendran P, Cha AC, Chin RK, Kim D, Adorno M, Raveh T, Tseng D, Jaiswal S, Enger PØ, Steinberg GK, Li G, So SK, Majeti R, Harsh GR, van de Rijn M, Teng NN, Sunwoo JB, Alizadeh AA, Clarke MF, Weissman IL. The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6662-7. 2. Liu J, Wang L, Zhao F, Tseng S, Narayanan C, Shura L, Willingham S, Howard M, Prohaska S, Volkmer J, Chao M, Weissman IL, Majeti R. Pre-Clinical Development of a Humanized Anti-CD47 Antibody with Anti-Cancer Therapeutic Potential. PLoS One. 2015 Sep 21;10(9):e0137345.Figure: CD47 is a myeloid-specific immune checkpoint. Figure 1Figure 2





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      SC14.05 - Tobacco Use and Immunotherapy (Now Available) (ID 6657)

      A. Dingemans

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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Author of

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    ISS01 - Industry Supported Symposium: Current and Emerging Treatments for Patients with ALK+ NSCLC – ARIAD Pharmaceuticals Inc. (ID 435)

    • Event: WCLC 2016
    • Type: Industry Supported Symposium
    • Track:
    • Presentations: 3
    • +

      ISS01.01 - Welcome & Introduction (ID 7135)

      C. Zielinski

      • Abstract

      Abstract not provided

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      ISS01.02 - ALK Inhibitors: Current Treatments and Sequencing (ID 7136)

      C. Zielinski

      • Abstract

      Abstract not provided

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      ISS01.05 - Summary and Conclusions (ID 7139)

      C. Zielinski

      • Abstract

      Abstract not provided

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    SC22 - Selection and Monitoring of Patients for Immune Checkpoint Inhibitors (ID 346)

    • Event: WCLC 2016
    • Type: Science Session
    • Track: Chemotherapy/Targeted Therapy/Immunotherapy
    • Presentations: 1
    • Now Available
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      SC22.04 - How Can Immunotherapy Be Implemented in a Cost-Effective Strategy? (Now Available) (ID 6693)

      C. Zielinski

      • Abstract
      • Presentation
      • Slides

      Abstract:
      “How Can Immunotherapy be Implemented In a Cost-Effective Strategy?” Christoph Zielinski, Director, Clinical Division of Oncology and Chairman, Department of Medicine I, and Comprehensive Cancer Center, Medical University Vienna – General Hospital, Vienna, Austria, Central European Cooperative Oncology Group (CECOG) When talking about immunotherapy and its cost-effectiveness, the story of disharmony between the magnitude of clinical benefit and the cost-effectiveness of certain drugs clearly emerges. I will try to illustrate this by the following arguments and data: The total health care costs of cancer per person varies widely within EU countries not only concerning outpatient and primary care, but also inpatient care and particularly drug expenditures. Cancer drug-related health care costs, thus differ between less than € 10.- per person up to over € 50.- per person. This divergence has been described previously and put into context with cancer outcomes (1) as well as cancer-associated mortality (2). Therefore, the European Society for Medical Oncology decided to create a magnitude of clinical benefit scale (ESMO-MCBS) “in order to promote high quality, rational, responsible and affordable cancer care wanting to highlight treatments which bring substantial improvements to the duration of survival and/or the quality of life of cancer patients” (3). It was intended that the scale was used for accelerated reimbursement evaluation. Factors taken into account for the ESMO-MCBS were particularly overall survival and/or progression-free survival as assessed by hazard ratios, quality of life, toxicity of the compound in question and the prognosis of the individual condition. Costs were not analysed in view of their significant heterogeneity across Europe. While generating two different scales for the curative versus the non-curative setting, a couple of rules were followed regarding the performed analyses: the priority was a strong level of evidence from large phase III studies with a careful analysis of each control arm and the identification of endpoints. For the required HR, the lower limit of the 95% CI was used to take into account the variability of the estimate. Before being published, the scale and its outcomes were broadly tested and evaluated in and by various institutions. The first full-length field testing (FT-MCBS) of the ESMO-MCBS was published recently (4) in which the results of non-small cell lung cancer (NSCLC) corresponded well with the original ESMO-MCBS. Regarding the use of the immune checkpoint inhibitor Nivolumab, the FT-MCBS generated the highest grade (i.e. “5”) for squamous NSCLC according to data generated within the Checkmate 017-Trial whereas a grade “4” was given for non-squamous NSCLC, as assessed in the Checkmate 057-Trial. Thus, the immune checkpoint inhibitor Nivolumab has acquired the highest or almost highest degree in the magnitude of clinical benefit, as assessed by the FT-MCBS scale. Soon after market introduction, concerns about the financial toxic dose of immune checkpoint inhibitors emerged leading to the rejection of NICE of Nivolumab in the second-line-treatment of NSCLC, whereas – in contrast - the Scottish authorities decided to include Nivolumab into their reimbursement strategies. Very recent analyses on this very topic showed that Nivolumab was not cost effective versus Docetaxel in the second-line-treatment of NSCLC based upon data generated in Checkmate 057-Trial. However, cost effectiveness could be very well reached by including and stratifying patients according to PD-L1 testing and the use of Nivolumab in PD-L1 overexpressing tumors on one side or – in statistical models - by the reduction of drug costs on the other. Either of these strategies would improve the cost effectiveness of Nivolumab (5, 6) Scientifically, however, the doubt remains to linger whether PD-L1 would be an optimal biomarker resulting in appropriate decision making for the choice of compound optimally suitable for the treatment of NSCLC without unjustly excluding patients who might have benefitted due to other factors from treatment: Thus, it is well known that certain somatic mutations occur more frequently in very special tumors than in others (7). Along this line, the efficacy of Nivolumab correlated with higher non-synonymous mutation burden in the Checkmate 063-Trial population (8). Therefore, it seems correct to conclude that we still have a long way to go to fully understand biomarkers predictive for the outcome of an optimal treatment of NSCLC with immune checkpoint inhibitors. Accordingly, appropriate analyses necessary for biomarker identification might translate into cost effectiveness. Such analyses might result in a primarily increased diagnostic cost, but lead to an ameliorated patient selection and, thus, ameliorated cost effectiveness in the appropriate use of immune checkpoint inhibitor treatment in NSCLC. In the meantime, the scientific community remains fascinated by the insights and results which are generated by the use of these compounds in a variety of diseases including NSCLC. References 1. Jedrzejewski M. et al., The Oncologist 20: 28, 2015; 2. .Ades F. et al., Ann. Oncol. 24: 2897, 2013; 3. N.I. Cherny et al., Ann. Oncol. 26: 1547, 2015; 4. B. Kiesewetter et al., ESMO Open 1: e000066, 2016; 5. K. Matter-Walstra et al., J. Thoracic Oncol., 2016, ePub.: http://dx.doi.org/10.1016/j.jtho.2016.05.032; 6. P.N. Aguiar et al., J. Clin. Oncol. 34, abstr. 9033, 2016; 7. L.B. Alexandrov et al., Nature. 22: 415, 2013; 8. N.A. Rizvi et al., Science 2015, ePub.: pii:aaa1348

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