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

  • 19895

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    139TiP - A non-interventional biomarker study in patients (pts) with non-small cell lung cancer (NSCLC) of adenocarcinoma histology who are treated with nintedanib according to the approved label (LUME-BioNIS) (ID 260)

    12:30 - 13:00  |  Author(s): N. Morsli
    • Abstract

    Background:
    Nintedanib+docetaxel significantly improved overall survival (OS) of pts with advanced adenocarcinoma NSCLC. There are currently no validated tumour- or serum-derived biomarkers to predict the efficacy of antiangiogenic therapy. The objective of this study is to investigate whether tumour-based gene/protein expression patterns or genomic markers, alone or combined with clinical covariates, could predict treatment effect in pts with adenocarcinoma NSCLC receiving nintedanib (Vargatef[®]).
    
    Trial design:
    In this non-interventional study at 86 mainly European sites, new biomarker data and clinical characteristics will be collected from ∼300 pts who receive nintedanib as part of routine treatment. Pts must be eligible for nintedanib+docetaxel, i.e. have advanced adenocarcinoma NSCLC after first-line chemotherapy, and will receive nintedanib 200 mg twice daily (Days 2–21 of 21-day cycle) and docetaxel (75 mg/m[2]; Day 1). The primary outcome is OS in relation to exploratory biomarker assessment, including gene expression profile, tumour genomic alterations and protein analysis. Tumour tissue samples obtained prior to first-line therapy are required along with informed consent. Mutation analysis of nintedanib target genes (VEGFR1–3, FGFR1–3, PDGFR α/β) and driver genes (EGFR, KRAS, ALK, BRAF, PIK3CA) will be conducted, as well as evaluation of tumour protein expression (e.g. PD-L1, CD133) and proliferation (Ki-67) markers by immunohistochemistry. One ∼2 mL blood sample (or a buccal swab) will be collected at baseline or after nintedanib initiation alongside routine blood sampling to analyse the potential influence of genetic variants in angiogenesis-related genes (e.g. single nucleotide polymorphisms in VEGFR1). Pts will be followed up every 6 months. The primary outcome will be analysed after 250 deaths. Gene expression patterns and tumour genomics in relation to efficacy will be analysed using univariate and multivariate regression models. Adverse events will be assessed. All analyses will be exploratory and considered hypothesis-generating. The study is ongoing (NCT02671422).
    
    Clinical trial identification:
    NCT02671422
    
    Legal entity responsible for the study:
    Boehringer Ingelheim Pharma GmbH & Co. KG
    
    Funding:
    Boehringer Ingelheim Pharma GmbH & Co. KG
    
    Disclosure:
    M. Reck: Author reports personal fees from Boehringer-Ingelheim, Hoffmann-La Roche, Lilly, MSD, BMS, AstraZeneca, Celgene, Merck and Pfizer. K. Kerr: Personal fees from Boehringer Ingelheim, during the conduct of the study. All other authors have declared no conflicts of interest.
    
    

  • 19925

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    170TiP - LUME-Meso: Randomised phase II/III study of nintedanib (N) + pemetrexed/cisplatin (PEM/CIS) followed by maintenance N or placebo (P) in chemo-naïve patients with malignant pleural mesothelioma (MPM) (ID 274)

    12:30 - 13:00  |  Author(s): N. Morsli
    • Abstract

    Background:
    PEM/CIS is the standard first-line treatment for MPM, with median overall survival (OS) of ∼1 year. N is a triple angiokinase inhibitor of vascular endothelial growth factor (VEGF) receptors 1–3, platelet-derived growth factor (PDGF) receptors α/β and fibroblast growth factor receptors 1–3, as well as Src and Abl kinases. VEGF and PDGF overexpression are associated with poor prognosis in MPM, and N has demonstrated efficacy in preclinical MPM models. We performed a randomised Phase II trial of N or P + PEM/CIS in MPM followed by maintenance N or P; progression-free survival (PFS) was the primary endpoint. An internal Data Monitoring Committee recommended the study be expanded to include a confirmatory Phase III part. With regulatory authority guidance, the Phase II data were unblinded, demonstrating a PFS benefit with N (hazard ratio 0.56, 95% confidence interval 0.34–0.91; p = 0.017); these data assisted in planning the Phase III part including sample size estimation, and N was granted U.S. Food & Drug Administration orphan drug designation for the treatment of MPM in December 2016. The Phase III part (NCT01907100) is recruiting.
    
    Trial design:
    For Phase III, 450 chemo-naïve patients worldwide (>100 sites in 27 countries) aged ≥18 years with unresectable MPM of epithelioid histology and Eastern Cooperative Oncology Group performance score 0–1 will be randomised 1:1 to receive up to 6 21-day cycles of PEM (500 mg/m[2])/CIS (75 mg/m[2]) on Day 1 plus N or P (200 mg twice daily, Days 2–21), followed by N or P monotherapy until disease progression or undue toxicity. The primary endpoint is PFS; the key secondary endpoint is OS. An adaptive design will be used at the time of the primary PFS analysis to reassess the number of OS events for sufficient OS power. Other secondary endpoints are objective response and disease control (using modified Response Evaluation Criteria in Solid Tumors). The frequency/severity of adverse events and health-related quality of life will also be assessed. An exploratory analysis of predictive/prognostic biomarkers is planned.
    
    Clinical trial identification:
    NCT01907100
    
    Legal entity responsible for the study:
    Boehringer Ingelheim Pharma GmbH & Co. KG
    
    Funding:
    Boehringer Ingelheim Pharma GmbH & Co. KG
    
    Disclosure:
    S. Popat: Acknowledges NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and the ICR, and is consultant to and has received honoraria from Boehringer Ingelheim and Eli Lilly. A. Nowak: Acknowledges funding from the National Health and Medical Research Council of Australia to the National Centre for Asbestos Related Diseases. A. Tsao: Received honoraria from Eli Lilly, Roche, Novartis, AstraZeneca, Ariad, Boehringer Ingelheim, Genentech, BMS, Seattle Genetics, and has received research funding from Eli Lilly, AstraZeneca, Millennium, BMS, Seattle Genetics, and Polaris. J. Van Meerbeeck: Received institutional funding through research grants from the Belgian Foundation against Cancer and Flemish Kom op tegen Kanker Fund. N. Vogelzang: Received an honorarium from Boehringer lngelheim for services on the steering committee of this study. D. Velema: Employee of Boehringer Ingelheim. N. Morsli: Employee of Boehringer Ingelheim. G. Scagliotti: Consultant for Eli Lilly and has received honoraria from Eli Lilly, Roche, Pfizer, Novartis, AstraZeneca, and Clovis Oncology. All other authors have declared no conflicts of interest.