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...

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Mesothelioma
Thoracic malignancies
Presenter Sanjay Popat
Citation Annals of Oncology (2017) 28 (suppl_2): ii56-ii58. 10.1093/annonc/mdx093
Authors S. Popat1, R. Gaafar2, A. Nowak3, A. Tsao4, J. Van Meerbeeck5, N. Vogelzang6, T. Nakano7, D. Velema8, N. Morsli9, G. Scagliotti10
  • 1Royal Marsden Hospital NHS Foundation Trust, SW3 6JJ - London/GB
  • 2National Cancer Institute, Cairo/EG
  • 3School Of Medicine And Pharmacology, The University of Western Australia, 6009 - Perth/AU
  • 4MD Anderson Cancer Center, Houston/US
  • 5Department Of Thoracic Oncology, Antwerp University Hospital, Edegem/BE
  • 6US Oncology Research c/o Comprehensive Cancer Crts of NV, Las Vegas/US
  • 7Hyogo College of Medicine, Nishinomiya/JP
  • 8Boehringer Ingelheim (Canada) Ltd./Ltée, Burlington/CA
  • 9Boehringer Ingelheim France S.A.S, Paris/FR
  • 10S. Luigi Hospital, Torino/IT

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/m2)/CIS (75 mg/m2) 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.