A Phase I Open-Label Dose Escalation Study of Intravenous INKmune In Patients With MDS or AML

Summary

INMB-INB16-002 is a Phase I open-label, dose escalation study of INKmune therapy in subjects with myelodysplastic syndrome (MDS) with excess blasts without Auer rods (EB-1 or 2, or CMML 1 or 2) or subjects with acute myeloid leukaemia (AML) in complete remission.

Timeline

Start

2020-06-15

Primary completion

2024-03-28

Completion

2024-04-26

Outcome

Outcome not reported

Stopped (Enrollment): “Slow/low Enrollment”

Publications

• Background Arai S, Meagher R, Swearingen M, Myint H, Rich E, Martinson J, Klingemann H. Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial. Cytotherapy. 2008;10(6):625-32. doi: 10.1080/14653240802301872.
• Background Bengala, C., V. Rasini, R. Sternieri, M. Dominici, A. Andreotti, R. Gelmini, L. Cafarelli, P. Bevini, A. Berti, and P. Conte. 2007. 'Phase I study of intraperitoneal MHC unrestricted adoptive cell therapy with TALL-104 cells in patients with peritoneal carcinosis', Journal of Clinical Oncology, 25: 3054-54.
• Background Bryceson YT, March ME, Ljunggren HG, Long EO. Activation, coactivation, and costimulation of resting human natural killer cells. Immunol Rev. 2006 Dec;214:73-91. doi: 10.1111/j.1600-065X.2006.00457.x.
• Background Carlsten M, Baumann BC, Simonsson M, Jadersten M, Forsblom AM, Hammarstedt C, Bryceson YT, Ljunggren HG, Hellstrom-Lindberg E, Malmberg KJ. Reduced DNAM-1 expression on bone marrow NK cells associated with impaired killing of CD34+ blasts in myelodysplastic syndrome. Leukemia. 2010 Sep;24(9):1607-16. doi: 10.1038/leu.2010.149. Epub 2010 Jul 8.
• Background Carlsten M, Norell H, Bryceson YT, Poschke I, Schedvins K, Ljunggren HG, Kiessling R, Malmberg KJ. Primary human tumor cells expressing CD155 impair tumor targeting by down-regulating DNAM-1 on NK cells. J Immunol. 2009 Oct 15;183(8):4921-30. doi: 10.4049/jimmunol.0901226.
• Background Cesano A, Santoli D. Two unique human leukemic T-cell lines endowed with a stable cytotoxic function and a different spectrum of target reactivity analysis and modulation of their lytic mechanisms. In Vitro Cell Dev Biol. 1992 Sep-Oct;28A(9-10):648-56. doi: 10.1007/BF02631041.
• Background Chandhok NS, Boddu PC, Gore SD, Prebet T. What are the most promising new agents in myelodysplastic syndromes? Curr Opin Hematol. 2019 Mar;26(2):77-87. doi: 10.1097/MOH.0000000000000483.
• Background Epling-Burnette PK, Bai F, Painter JS, Rollison DE, Salih HR, Krusch M, Zou J, Ku E, Zhong B, Boulware D, Moscinski L, Wei S, Djeu JY, List AF. Reduced natural killer (NK) function associated with high-risk myelodysplastic syndrome (MDS) and reduced expression of activating NK receptors. Blood. 2007 Jun 1;109(11):4816-24. doi: 10.1182/blood-2006-07-035519. Epub 2007 Mar 6.
• Background Fehniger TA, Miller JS, Stuart RK, Cooley S, Salhotra A, Curtsinger J, Westervelt P, DiPersio JF, Hillman TM, Silver N, Szarek M, Gorelik L, Lowdell MW, Rowinsky E. A Phase 1 Trial of CNDO-109-Activated Natural Killer Cells in Patients with High-Risk Acute Myeloid Leukemia. Biol Blood Marrow Transplant. 2018 Aug;24(8):1581-1589. doi: 10.1016/j.bbmt.2018.03.019. Epub 2018 Mar 27.
• Background Fozza C. The burden of autoimmunity in myelodysplastic syndromes. Hematol Oncol. 2018 Feb;36(1):15-23. doi: 10.1002/hon.2423. Epub 2017 Apr 27.
• Background Gong JH, Maki G, Klingemann HG. Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. Leukemia. 1994 Apr;8(4):652-8.
• Background Hou HA, Tsai CH, Lin CC, Chou WC, Kuo YY, Liu CY, Tseng MH, Peng YL, Liu MC, Liu CW, Liao XW, Lin LI, Yao M, Tang JL, Tien HF. Incorporation of mutations in five genes in the revised International Prognostic Scoring System can improve risk stratification in the patients with myelodysplastic syndrome. Blood Cancer J. 2018 Apr 4;8(4):39. doi: 10.1038/s41408-018-0074-7.
• Background Kiladjian JJ, Bourgeois E, Lobe I, Braun T, Visentin G, Bourhis JH, Fenaux P, Chouaib S, Caignard A. Cytolytic function and survival of natural killer cells are severely altered in myelodysplastic syndromes. Leukemia. 2006 Mar;20(3):463-70. doi: 10.1038/sj.leu.2404080.
• Background Kottaridis PD, North J, Tsirogianni M, Marden C, Samuel ER, Jide-Banwo S, Grace S, Lowdell MW. Two-Stage Priming of Allogeneic Natural Killer Cells for the Treatment of Patients with Acute Myeloid Leukemia: A Phase I Trial. PLoS One. 2015 Jun 10;10(6):e0123416. doi: 10.1371/journal.pone.0123416. eCollection 2015.
• Background Lanier LL. Up on the tightrope: natural killer cell activation and inhibition. Nat Immunol. 2008 May;9(5):495-502. doi: 10.1038/ni1581.
• Background Loghavi S, Sui D, Wei P, Garcia-Manero G, Pierce S, Routbort MJ, Jabbour EJ, Pemmaraju N, Kanagal-Shamanna R, Gur HD, Hu S, Zuo Z, Medeiros LJ, Kantarjian HM, Khoury JD. Validation of the 2017 revision of the WHO chronic myelomonocytic leukemia categories. Blood Adv. 2018 Aug 14;2(15):1807-1816. doi: 10.1182/bloodadvances.2018019224.
• Background Lucas M, Schachterle W, Oberle K, Aichele P, Diefenbach A. Dendritic cells prime natural killer cells by trans-presenting interleukin 15. Immunity. 2007 Apr;26(4):503-17. doi: 10.1016/j.immuni.2007.03.006. Epub 2007 Mar 29.
• Background Nazha A, Bejar R. Molecular Data and the IPSS-R: How Mutational Burden Can Affect Prognostication in MDS. Curr Hematol Malig Rep. 2017 Oct;12(5):461-467. doi: 10.1007/s11899-017-0407-9.
• Background North J, Bakhsh I, Marden C, Pittman H, Addison E, Navarrete C, Anderson R, Lowdell MW. Tumor-primed human natural killer cells lyse NK-resistant tumor targets: evidence of a two-stage process in resting NK cell activation. J Immunol. 2007 Jan 1;178(1):85-94. doi: 10.4049/jimmunol.178.1.85.
• Background Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, Van Loo P, Yoon CJ, Ellis P, Wedge DC, Pellagatti A, Shlien A, Groves MJ, Forbes SA, Raine K, Hinton J, Mudie LJ, McLaren S, Hardy C, Latimer C, Della Porta MG, O'Meara S, Ambaglio I, Galli A, Butler AP, Walldin G, Teague JW, Quek L, Sternberg A, Gambacorti-Passerini C, Cross NC, Green AR, Boultwood J, Vyas P, Hellstrom-Lindberg E, Bowen D, Cazzola M, Stratton MR, Campbell PJ; Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013 Nov 21;122(22):3616-27; quiz 3699. doi: 10.1182/blood-2013-08-518886. Epub 2013 Sep 12.
• Background Sabry M, Lowdell MW. Tumor-primed NK cells: waiting for the green light. Front Immunol. 2013 Nov 25;4:408. doi: 10.3389/fimmu.2013.00408.
• Background Sabry M, Zubiak A, Hood SP, Simmonds P, Arellano-Ballestero H, Cournoyer E, Mashar M, Pockley AG, Lowdell MW. Tumor- and cytokine-primed human natural killer cells exhibit distinct phenotypic and transcriptional signatures. PLoS One. 2019 Jun 26;14(6):e0218674. doi: 10.1371/journal.pone.0218674. eCollection 2019.
• Background Tsirogianni M, Grigoriou E, Kapsimalli V, Dagla K, Stamouli M, Gkirkas K, Konsta E, Karagiannidou A, Gkodopoulos K, Stavroulaki G, Pappa V, Angelopoulou M, Lowdell M, Tsirigotis P. Natural killer cell cytotoxicity is a predictor of outcome for patients with high risk myelodysplastic syndrome and oligoblastic acute myeloid leukemia treated with azacytidine. Leuk Lymphoma. 2019 Oct;60(10):2457-2463. doi: 10.1080/10428194.2019.1581935. Epub 2019 Apr 5.
• Background Tonn T, Schwabe D, Klingemann HG, Becker S, Esser R, Koehl U, Suttorp M, Seifried E, Ottmann OG, Bug G. Treatment of patients with advanced cancer with the natural killer cell line NK-92. Cytotherapy. 2013 Dec;15(12):1563-70. doi: 10.1016/j.jcyt.2013.06.017. Epub 2013 Oct 1.
• Background Visonneau S, Cesano A, Porter DL, Luger SL, Schuchter L, Kamoun M, Torosian MH, Duffy K, Sickles C, Stadtmauer EA, Santoli D. Phase I trial of TALL-104 cells in patients with refractory metastatic breast cancer. Clin Cancer Res. 2000 May;6(5):1744-54.
• Background Williams BA, Law AD, Routy B, denHollander N, Gupta V, Wang XH, Chaboureau A, Viswanathan S, Keating A. A phase I trial of NK-92 cells for refractory hematological malignancies relapsing after autologous hematopoietic cell transplantation shows safety and evidence of efficacy. Oncotarget. 2017 Jul 12;8(51):89256-89268. doi: 10.18632/oncotarget.19204. eCollection 2017 Oct 24.

Drugs

Indications