Study Protocol: Phase-Ib Trial of Nivolumab Combined With Metformin for Refractory/Recurrent Solid Tumors

Clinical Lung Cancer
Toshio KuboKatsuyuki Kiura

Abstract

Although immune checkpoint inhibitors have shown significant survival benefits in the treatment of several cancers, optimal outcomes have been limited to certain subsets of patients. In a previous study, we found that the addition of metformin to nivolumab, an anti-programmed cell death protein 1 (PD-1) antibody, yielded substantial tumor regression in mouse models. Further analysis revealed that the number of tumor-infiltrating CD8 T cells had increased markedly. Based on this result, we have launched an investigator-initiated open-label phase-Ib clinical trial. The objectives of this trial are to investigate the safety, efficacy, and pharmacokinetics of a metformin-nivolumab combination treatment. This study consists of 2 parts. The recommended dose of metformin combined with nivolumab is determined in part 1. The safety and efficacy of the optimal dose of metformin to be delivered in conjunction with nivolumab are examined in part 2. Patient eligibility is based on the following criteria: pathologic diagnosis of refractory/recurrent solid tumor (part 1), and non-small-cell lung cancer or pancreatic cancer refractory to standard primary treatment (part 2); no prior use of immune checkpoint inhibitor; performance status 0 or 1...Continue Reading

References

Sep 15, 2005·Annals of Oncology : Official Journal of the European Society for Medical Oncology·K HottaM Tanimoto
Jun 25, 2010·The New England Journal of Medicine·Makoto MaemondoUNKNOWN North-East Japan Study Group
May 23, 2014·JAMA : the Journal of the American Medical Association·Mark G KrisPaul A Bunn
Sep 30, 2014·The New England Journal of Medicine·Alice T ShawA John Iafrate
Nov 18, 2014·The New England Journal of Medicine·Caroline RobertPaolo A Ascierto
Jan 28, 2015·Proceedings of the National Academy of Sciences of the United States of America·Shingo EikawaHeiichiro Udono
Jun 2, 2015·The New England Journal of Medicine·Julie BrahmerDavid R Spigel
Sep 26, 2015·The New England Journal of Medicine·Robert J MotzerUNKNOWN CheckMate 025 Investigators
Sep 29, 2015·The New England Journal of Medicine·Hossein BorghaeiJulie R Brahmer
Dec 13, 2016·Cancer Immunology Research·Nicole E ScharpingGreg M Delgoffe

❮ Previous
Next ❯

Citations

Jun 24, 2020·Human Vaccines & Immunotherapeutics·Nadiya HussainDavid J Pinato
May 16, 2019·Cellular and Molecular Life Sciences : CMLS·Winnie Fong, Kenneth K W To
Oct 28, 2019·Oncoimmunology·Sara VerduraJavier A Menendez
Jan 19, 2020·Nature Reviews. Urology·Julieta AfonsoFátima Baltazar
Jul 25, 2021·Cancers·Julien AncelValérian Dormoy

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.