Advertisement

Cancer Immunology, Immunotherapy

, Volume 68, Issue 1, pp 143–150 | Cite as

The Italian Network for Tumor Bio-Immunotherapy (NIBIT) Foundation: ongoing and prospective activities in immuno-oncology

  • Anna Maria Di GiacomoEmail author
  • Alessia Covre
  • Gianluca Giacobini
  • Ramy Ibrahim
  • Jaclyn Lyman
  • Pier Giorgio Natali
  • Michele Maio
Focussed Research Review
  • 179 Downloads

Abstract

The ongoing revolution in cancer immunotherapy stems from the knowledge that distinct immune-checkpoints regulate the physiological crosstalk between and among immune cells by delivering inhibitory or activating signals. These notions, and the availability of mAb directed to diverse immune-checkpoint molecules, have led to a significant clinical improvement in cancer treatment. In this scenario, further achievements are undoubtedly to be expected from the contribution of novel, proof-of-principle clinical trials designed to explore the therapeutic efficacy of new immunotherapy-based combinations and treatment sequences. Along these lines, the clinical translation of pre-clinical evidence generated by non-profit research entities is likely to provide a significant contribution to gaining new insights that will further boost the field of cancer immunotherapy. To pursue this goal, and to provide comprehensive educational programs in immune-oncology (I-O), several national and global networks have been revitalized or newly established in recent years. This rapidly evolving scenario led the Board of Directors of the Italian Network of Tumor Bio-Immunotherapy (NIBIT) to establish the NIBIT Foundation. This Focused Research Review summarizes the main ongoing and prospective I-O activities of the NIBIT Foundation.

Keywords

Immunotherapy Immune-oncology Melanoma Mesothelioma Clinical trials NIBIT 

Abbreviations

BM

Brain metastasis

CII

Cancer immunology, immunotherapy

CIO

Center for immuno-oncology

CNS

Central nervous system

CRI

Cancer research institute

DCR

Disease control rate

DHA

DNA hypomethylating agents

DL

Dose level

DOR

Duration of response

IITs

Investigator-initiated trials

I-O

Immuno-Oncology

ir

Immune-related

MM

Metastatic melanoma

MMESO

Malignant mesothelioma

MTD

Maximum tolerated dose

NIBIT

Network Italiano per la Bioterapia dei Tumori (Italian Network for Tumor Bio-Immunotherapy)

ORR

Objective response rate

PFS

Progression-free survival

PICI

Parker Institute for Cancer Immunotherapy

TESLA

Tumor neoantigEn SeLection Alliance

UHS

University Hospital of Siena

W

Week

WIC

World Immunotherapy Council

Notes

Acknowledgements

The authors would like to thank the PICI’s medical writer who did the final language editing of the manuscript.

Author contributions

AMDG and MM wrote the first draft of this paper based in part on the talks of RI at the NIBIT 2017 meeting in Siena. AC and GG wrote the section “Educational Activities”. JL and RI wrote the section “Collaboration with the Parker Institute for Cancer Immunotherapy” PGN revised the manuscript. All authors critically discussed the manuscript, contributed to its contents, and checked and approved the final version.

Funding

This work was supported in part by the NIBIT Foundation and by the Associazione Italiana per la Ricerca sul Cancro (IG 2014 ID 15373; IG 06/30/C/9).

Compliance with ethical standards

Conflict of interest

Anna Maria Di Giacomo served on the advisory board of Bristol-Myers Squibb, Incyte, Pierre Fabre, Glaxo Smith Kline and she is a member of the scientific board of directors of the NIBIT Foundation; Ramy Ibrahim is a member of the scientific advisory board of: Arcus, Harpoon, Immunovaccine and ImaginAB;Jaclyn Lyman is a PICI employee; Pier Giorgio Natali is a member of the scientific board of directors of the NIBIT Foundation; Michele Maio served on advisory boards of Bristol-Myers Squibb, Roche-Genentech, Merck Sharp Dohme and AstraZeneca-MedImmune, and he is the president of the NIBIT Foundation. The authors declare that there are no other conflicts of interest.

References

  1. 1.
    Maio M, Fonsatti E (2014) The Italian Network for Tumor Biotherapy (NIBIT): past, present and future goals. Rev Health Care 5(1):3–6.  https://doi.org/10.7175/rhc.v5i1.896 CrossRefGoogle Scholar
  2. 2.
    Maio M, Lofiego MF, Fazio C, Cannito S, Chiarucci C, Giacobini G, Valente M, Tunici P, Covre A, Russo V (2018) Fifteenth Meeting of the Network Italiano per la Bioterapia dei Tumori (NIBIT) on Cancer Bio-Immunotherapy, Siena, Italy, October 5–7, 2017. Cancer Immunol Immunother.  https://doi.org/10.1007/s00262-018-2222-0 CrossRefPubMedGoogle Scholar
  3. 3.
    Korn EL, Liu PY, Lee SJ, Chapman JA, Niedzwiecki D, Suman VJ, Moon J, Sondak VK, Atkins MB, Eisenhauer EA, Parulekar W, Markovic SN, Saxman S, Kirkwood JM (2008) Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol 1 26(4):527–534.  https://doi.org/10.1200/JCO.2007.12.7837 CrossRefPubMedGoogle Scholar
  4. 4.
    Margolin K, Ernstoff MS, Hamid O, Lawrence D, McDermott D, Puzanov I, Wolchok JD, Clark JI, Sznol M, Logan TF, Richards J, Michener T, Balogh A, Heller KN, Hodi FS (2012) Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol 13:459–465.  https://doi.org/10.1016/S1470-2045(12)70090-6 CrossRefPubMedGoogle Scholar
  5. 5.
    Di Giacomo AM, Ascierto PA, Pilla L, Santinami M, Ferrucci PF, Giannarelli D, Marasco A, Rivoltini L, Simeone E, Nicoletti SV, Fonsatti E, Annesi D, Queirolo P, Testori A, Ridolfi R, Parmiani G, Maio M (2012) Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1): an open-label, single-arm phase 2 trial. Lancet Oncol 13:879–886.  https://doi.org/10.1016/S1470-2045(12)70324-8 CrossRefPubMedGoogle Scholar
  6. 6.
    Maio M, Grob JJ, Aamdal S, Bondarenko I, Robert C, Thomas L, Garbe C, Chiarion-Sileni V, Testori A, Chen TT, Tschaika M, Wolchok JD (2015) Five-year survival rates for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a phase III trial. J Clin Oncol. 33(10):1191–1196.  https://doi.org/10.1200/JCO.2014.56.6018 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Di Giacomo AM, Ascierto PA, Queirolo P, Pilla L, Ridolfi R, Santinami M, Testori A, Simeone E, Guidoboni M, Maurichi A, Orgiano L, Spadola G, Del Vecchio M, Danielli R, Calabrò L, Annesi D, Giannarelli D, Maccalli C, Fonsatti E, Parmiani G, Maio M (2015) Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian Network for Tumor Biotherapy (NIBIT)-M1 phase II study. Ann Oncol 26(4):798–803.  https://doi.org/10.1093/annonc/mdu577 CrossRefPubMedGoogle Scholar
  8. 8.
    Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2 373(1):23–34.  https://doi.org/10.1056/NEJMoa1504030 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Di Giacomo AM (2015) A randomized, phase III study of fotemustine versus the combination of fotemustine and ipilimumab or the combination of ipilimumab and nivolumab in patients with metastatic melanoma with brain metastasis: the NIBIT-M2 trial. J Clin Oncol.  https://doi.org/10.1200/jco.2015.33.15_suppl.tps9090 CrossRefGoogle Scholar
  10. 10.
    Long GV, Atkinson V, Lo S, Sandhu S, Guminski AD, Brown MP, Wilmott JS, Edwards J, Gonzalez M, Scolyer RA, Menzies AM, McArthur GA (2018) Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multi centre randomised phase 2 study. Lancet Oncol 19(5):672–681.  https://doi.org/10.1016/S1470-2045(18)30139-6 CrossRefGoogle Scholar
  11. 11.
    Tawbi HAH, Forsyth PAJ, Algazi AP, Hamid O, Hodi FS, Moschos SJ, Khushalani N, Gonzalez R, Lao C, Postow M, Atkins MB, Ernstoff M, Puzanov I, Kudchadkar R, Thomas R, Tarhini A, Jiang J, Avila A, Demelo S, Margolin K (2017) Efficacy and safety of nivolumab (NIVO) plus ipilimumab (IPI) in patients with melanoma (MEL) metastatic to the brain: Results of the phase II study CheckMate 204. J Clin Oncol.  https://doi.org/10.1200/JCO.2017.35.15_suppl.9507 CrossRefGoogle Scholar
  12. 12.
    Chatterjee A, Rodger EJ, Eccles MR (2017) Epigenetic drivers of tumourigenesis and cancer metastasis. Semin Cancer Biolpii.  https://doi.org/10.1016/j.semcancer.2017.08.004 CrossRefGoogle Scholar
  13. 13.
    Maio M, Covre A, Fratta E, Di Giacomo AM, Taverna P, Natali PG, Coral S, Sigalotti L (2015) Molecular pathways: at the crossroads of cancer epigenetics and immunotherapy. Clin Cancer Res 21(18):4040–4047.  https://doi.org/10.1158/1078-0432.CCR-14-2914 CrossRefPubMedGoogle Scholar
  14. 14.
    Sigalotti L, Fratta E, Coral S, Maio M (2014) Epigenetic drugs as immunomodulators for combination therapies in solid tumors. Pharmacol Ther 142(3):339–350.  https://doi.org/10.1016/j.pharmthera.2013.12.015 CrossRefPubMedGoogle Scholar
  15. 15.
    Covre A, Coral S, Di Giacomo AM, Taverna P, Azab M, Maio M (2015) Epigenetics meets immune checkpoints. Semin Oncol 42(3):506–513.  https://doi.org/10.1053/j.seminoncol.2015.02.003 CrossRefPubMedGoogle Scholar
  16. 16.
    Di Giacomo AM, Covre A, Taverna P, Coral S, Amato G, Keer HN, Lowder J, Giannarelli D, Azab M, Maio M (2016) A phase Ib study combining the second-generation DNA hypomethylating agent (DHA) guadecitabine (SGI-110) and ipilimumab in patients with metastatic melanoma: The NIBIT-M4 study. J Clin Oncol.  https://doi.org/10.1200/JCO.2016.34.15_suppl.TPS9595 CrossRefGoogle Scholar
  17. 17.
    Di Giacomo AM, Covre A, Finotello F, Rieder D, Sigalotti L, Fazio C, Cutaia O, Bock C, Petitprez F, Lacroix L, Lowder J, Fridman WH, Sautès-Fridman C, Trajanoski Z, Maio M (2018) Epigenetic tumor remodelling to improve the efficacy of immune checkpoint blockade: the NIBIT-M4 clinical trial. Cancer Res 78(13 Supplement):CT059.  https://doi.org/10.1158/1538-7445.AM2018-CT059 CrossRefGoogle Scholar
  18. 18.
    Issa JJ, Roboz G, Rizzieri D, Jabbour E, Stock W, O’Connell C, Yee K, Tibes R, Griffiths EA, Walsh K, Daver N, Chung W, Naim S, Taverna P, Oganesian A, Hao Y, Lowder JN, Azab M, Kantarjian H (2015) Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study. Lancet Oncol 16(9):1099–1110.  https://doi.org/10.1016/S1470-2045(15)00038-8 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Calabrò L, Morra A, Fonsatti E, Cutaia O, Amato G, Giannarelli D, Di Giacomo AM, Danielli R, Altomonte M, Mutti L, Maio M (2013) Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial. Lancet Oncol 14(11):1104–1111.  https://doi.org/10.1016/S1470-2045(13)70381-4 CrossRefPubMedGoogle Scholar
  20. 20.
    Calabrò L, Morra A, Fonsatti E, Cutaia O, Fazio C, Annesi D, Lenoci M, Amato G, Danielli R, Altomonte M, Giannarelli D, Di Giacomo AM, Maio M (2015) Efficacy and safety of an intensified schedule of tremelimumab for chemotherapy-resistant malignant mesothelioma: an open-label, single-arm, phase 2 study. Lancet Respir Med 3(4):301–309.  https://doi.org/10.1016/S2213-2600(15)00092-2 CrossRefPubMedGoogle Scholar
  21. 21.
    Alley EW, Lopez J, Santoro A, Morosky A, Saraf S, Piperdi B, van Brummelen E (2018) Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Lancet Oncol 18(5):623–630.  https://doi.org/10.1016/S1470-2045(17)30169-9 CrossRefGoogle Scholar
  22. 22.
    Quispel-Janssen J, van der Noort V, de Vries JF, Zimmerman M, Lalezari F, Thunnissen E, Monkhorst K, Schouten R, Schunselaar L, Disselhorst M, Klomp H, Hartemink K, Burgers S, Buikhuisen W, Baas P (2018) PD-1 blockade with nivolumab in patients with recurrent Malignant Pleural Mesothelioma. J Thorac Oncol.  https://doi.org/10.1016/j.jtho.2018.05.038 CrossRefPubMedGoogle Scholar
  23. 23.
    Calabrò L, Morra A, Giannarelli D, Amato G, D’Incecco A, Covre A, Lewis A, Rebelatto MC, Danielli R, Altomonte M, Di Giacomo AM, Maio M (2018) Tremelimumab combined with durvalumab in patients with mesothelioma (NIBIT-MESO-1): an open-label, non-randomised, phase 2study. Lancet Respir Med 6(6):451–460.  https://doi.org/10.1016/S2213-2600(18)30151-6 CrossRefPubMedGoogle Scholar
  24. 24.
    Calabrò L, Morra A, Cornelissen R, Aerts J, Maio M (2018) Immune checkpoint blockade therapy of mesothelioma: a clinical and radiological challenge. Cancer Immunol Immunother.  https://doi.org/10.1007/s00262-018-2191-3 CrossRefPubMedGoogle Scholar
  25. 25.
    Russo V, Chiarucci C, Lofiego MF, Fazio C, Bertocci E, Cutaia O, Giacobini G, Lazzeri A, Lamboglia A, Altomonte M, Tunici P, Covre A, Maio M (2018) Fourteenth meeting of the network Italiano per la Bioterapia dei Tumori (NIBIT) on cancer bio-immunotherapy, Siena, Italy, October 13–15, 2016. Cancer Immunol Immunother 67(6):1023–1030.  https://doi.org/10.1007/s00262-017-2078-8 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Anna Maria Di Giacomo
    • 1
    Email author
  • Alessia Covre
    • 1
  • Gianluca Giacobini
    • 1
  • Ramy Ibrahim
    • 2
  • Jaclyn Lyman
    • 2
  • Pier Giorgio Natali
    • 3
  • Michele Maio
    • 1
  1. 1.Center for Immuno-Oncology, Medical Oncology and ImmunotherapyUniversity Hospital of Siena, Istituto Toscano TumoriSienaItaly
  2. 2.Parker Institute for Cancer ImmunotherapySan FranciscoUSA
  3. 3.Center on Aging Sciences and Translational Medicine (CeSI-MeT)Gabriele d’ Annunzio UniversityChietiItaly

Personalised recommendations