Preclinical Characterization of Linrodostat Mesylate, a Novel, Potent, and Selective Oral Indoleamine 2,3-Dioxygenase 1 Inhibitor.
Journal
Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
03
04
2020
revised:
11
09
2020
accepted:
02
12
2020
pubmed:
11
12
2020
medline:
3
11
2021
entrez:
10
12
2020
Statut:
ppublish
Résumé
Tumors can exploit the indoleamine 2,3-dioxygenase 1 (IDO1) pathway to create an immunosuppressive microenvironment. Activated IDO1 metabolizes tryptophan into immunosuppressive kynurenine, leading to suppressed effector T-cell (Teff) proliferation, allowing for tumor escape from host immune surveillance. IDO1 inhibition counteracts this immunosuppressive tumor microenvironment and may improve cancer outcomes, particularly when combined with other immunotherapies. Linrodostat mesylate (linrodostat) is a potent, selective oral IDO1 inhibitor that occupies the heme cofactor-binding site to prevent further IDO1 activation and is currently in multiple clinical trials for treatment of patients with advanced cancers. Here, we assess the
Identifiants
pubmed: 33298590
pii: 1535-7163.MCT-20-0251
doi: 10.1158/1535-7163.MCT-20-0251
doi:
Substances chimiques
Acetamides
0
Indoleamine-Pyrrole 2,3,-Dioxygenase
0
Quinolines
0
linrodostat
0A7729F42K
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
467-476Informations de copyright
©2020 American Association for Cancer Research.
Références
Labadie BW, Bao R, Luke JJ. Reimagining IDO pathway inhibition in cancer immunotherapy via downstream focus on the tryptophan-kynurenine-aryl hydrocarbon axis. Clin Cancer Res. 2019;25:1462–71.
Nelp MT, Kates PA, Hunt JT, Newitt JA, Balog A, Maley D, et al. Immune-modulating enzyme indoleamine 2,3-dioxygenase is effectively inhibited by targeting its apo-form. Proc Natl Acad Sci U S A. 2018;115:3249–54.
Moffett JR, Namboodiri MA. Tryptophan and the immune response. Immunol Cell Biol. 2003;81:247–65.
Liu M, Wang X, Wang L, Ma X, Gong Z, Zhang S, et al. Targeting the IDO1 pathway in cancer: from bench to bedside. J Hematol Oncol. 2018;11:100.
Belir C, Sarisozen C. Indoleamine 2,3-dioxygenase (IDO): only an enzyme or a checkpoint controller?. J Oncol Sci. 2017;3:52–6.
Moon YW, Hajjar J, Hwu P, Naing A. Targeting the indoleamine 2,3-dioxygenase pathway in cancer. J Immunother Cancer. 2015;3:51.
Munn DH, Zhou M, Attwood JT, Bondarev I, Conway SJ, Marshall B, et al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science. 1998;281:1191–3.
Heitger A. Regulation of expression and function of IDO in human dendritic cells. Curr Med Chem. 2011;18:2222–33.
Maliniemi P, Laukkanen K, Vakeva L, Dettmer K, Lipsanen T, Jeskanen L, et al. Biological and clinical significance of tryptophan-catabolizing enzymes in cutaneous T-cell lymphomas. Oncoimmunology. 2017;6:e1273310.
Godin-Ethier J, Hanafi LA, Piccirillo CA, Lapointe R. Indoleamine 2,3-dioxygenase expression in human cancers: clinical and immunologic perspectives. Clin Cancer Res. 2011;17:6985–91.
Masaki A, Ishida T, Maeda Y, Suzuki S, Ito A, Takino H, et al. Prognostic significance of tryptophan catabolism in adult T-cell leukemia/lymphoma. Clin Cancer Res. 2015;21:2830–9.
Theate I, van Baren N, Pilotte L, Moulin P, Larrieu P, Renauld JC, et al. Extensive profiling of the expression of the indoleamine3-dioxygenase 1 protein in normal and tumoral human tissues. Cancer Immunol Res. 2015;3:161–72.
Ino K, Yamamoto E, Shibata K, Kajiyama H, Yoshida N, Terauchi M, et al. Inverse correlation between tumoral indoleamine 2,3-dioxygenase expression and tumor-infiltrating lymphocytes in endometrial cancer: its association with disease progression and survival. Clin Cancer Res. 2008;14:2310–7.
Takao M, Okamoto A, Nikaido T, Urashima M, Takakura S, Saito M, et al. Increased synthesis of indoleamine-2,3-dioxygenase protein is positively associated with impaired survival in patients with serous-type, but not with other types of, ovarian cancer. Oncol Rep. 2007;17:1333–9.
Hunt JT, Balog A, Huang C, Lin T-A, Lin T-A, Maley D, et al. Structure, in vitro biology and in vivo pharmacodynamic characterization of a novel clinical IDO1 inhibitor (abstr). Presented at the Proceedings of the AACR Annual Meeting; April 1–5. 20172017;77.
An investigational immuno-therapy study of BMS-986205 given in combination with nivolumab and in combination with both nivolumab and ipilimumab in cancers that are advanced or have spread.
Siu LL, Gelmon K, Chu Q, Pachynski R, Alese O, Basciano P, et al. BMS-986205, an optimized indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, is well tolerated with potent pharmacodynamic (PD) activity, alone and in combination with nivolumab (nivo) in advanced cancers in a phase 1/2a trial (abstr). Presented at the Proceedings of the AACR Annual Meeting; April 1–5, 2017; Washington, DC. 2017;77.
Beatty GL, O'Dwyer PJ, Clark J, Shi JG, Bowman KJ, Scherle PA, et al. First-in-human phase i study of the oral inhibitor of indoleamine 2,3-dioxygenase-1 epacadostat (INCB024360) in patients with advanced solid malignancies. Clin Cancer Res. 2017;23:3269–76.
Soliman HH, Minton SE, Han HS, Ismail-Khan R, Neuger A, Khambati F, et al. A phase I study of indoximod in patients with advanced malignancies. Oncotarget. 2016;7:22928–38.
Muller AJ, DuHadaway JB, Donover PS, Sutanto-Ward E, Prendergast GC. Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat Med. 2005;11:312–9.
Tabernero J, Luke JJ, Joshua AM, Varga AI, Moreno V, Desai J, et al. BMS-986205, an indoleamine 2,3-dioxygenase 1 inhibitor (IDO1i), in combination with nivolumab (NIVO): Updated safety across all tumor cohorts and efficacy in pts with advanced bladder cancer (advBC). J Clin Oncol. 2018;27.
Resch I, Shariat SF, Gust KM. PD-1 and PD-L1 inhibitors after platinum-based chemotherapy or in first-line therapy in cisplatin-ineligible patients. Memo. 2018;11:43–6.
Long GV, Dummer R, Hamid O, Gajewski TF, Caglevic C, Dalle S, et al. Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study. Lancet Oncol. 2019;20:1083–97.
A study of BMS-986205 alone and in combination with nivolumab in Chinese patients with advanced malignant solid tumors.
A study of chemo only versus chemo plus nivo with or without BMS-986205, followed by post- surgery therapy with nivo or nivo and BMS-986205 in patients with MIBC.
A study of nivolumab or nivolumab plus experimental medication BMS-986205 with or without bacillus Calumette-Guerin (BCG) in BCG unresponsive bladder cancer that has not invaded into the muscle wall of the bladder (CheckMate 9UT).
An investigational immuno-therapy study of BMS-986205 combined with nivolumab, compared to nivolumab by itself, in patients with advanced melanoma.
A study of BMS-986205 given in combination with nivolumab in patients with advanced tumors.
Luke JJ, Tabernero J, Gelmon KA, Varga AI, Moreno V, Desai J, et al. BMS-986205, an indoleamine 2,3-dioxygenase 1 inhibitor, plus nivolumab: updated safety across all tumor cohorts and efficacy in advanced bladder cancer (abstr). Presented at the Proceedings of the American Urological Association Annual Meeting; May 3–6, 2019; Chicago, IL..
Luke JJ, Siu LL, Santucci-Pereira J, Nelson D, Kandoussi EE, Fischer B, et al. Interferon γ (IFN-γ) gene signature and tryptophan 2,3-dioxygenase 2 (TDO2) gene expression: a potential predictive composite biomarker for linrodostat mesylate (BMS-986205; indoleamine 2,3-dioxygenase 1 inhibitor [IDO1i]) + nivolumab (NIVO). Ann Oncol. 2019;30:v760–96.
Luke JJ, Gelmon K, Pachynski RK, Desai J, Moreno V, Tabernero J, et al. Preliminary antitumor and immunomodulatory activity of BMS-986205, an optimized indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, in combination with nivolumab in patients with advanced cancers. J Immunother Cancer. 2017;5.
Beck HP, Jaen JC, Osipov M, Powers JP, Balog JA, Cherney EC, et al. Immunoregulatory agents. Patent Cooperation Treaty Int Appl WO 2016073774. 2016.
Fraunhoffer KJ, DelMonte AJ, Beutner GL, Bultman MS, Camacho K, Cohen B, et al. Rapid development of a commercial process for linrodostat, an indoleamine 2,3-dioxygenase (IDO) inhibitor. Org Proc Res Dev. 2019;23:2482–98.
Sugimoto H, Oda S, Otsuki T, Hino T, Yoshida T, Shiro Y. Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase. Proc Natl Acad Sci U S A. 2006;103:2611–6.
Kumar S, Jaller D, Patel B, LaLonde JM, DuHadaway JB, Malachowski WP, et al. Structure based development of phenylimidazole-derived inhibitors of indoleamine 2,3-dioxygenase. J Med Chem. 2008;51:4968–77.
Yue EW, Sparks R, Polam P, Modi D, Douty B, Wayland B, et al. INCB24360 (epacadostat), a highly potent and selective indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor for immuno-oncology. ACS Med Chem Lett. 2017;8:486–91.
Yamamoto R, Yamamoto Y, Imai S, Fukutomi R, Ozawa Y, Abe M, et al. Effects of various phytochemicals on indoleamine3-dioxygenase 1 activity: galanal is a novel, competitive inhibitor of the enzyme. PLoS One. 2014;9:e88789.
Ebert PS, Hess RA, Frykholm BC, Tschudy DP. Succinylacetone, a potent inhibitor of heme biosynthesis: effect on cell growth, heme content and delta-aminolevulinic acid dehydratase activity of malignant murine erythroleukemia cells. Biochem Biophys Res Commun. 1979;88:1382–90.
Giger U, Meyer UA. Induction of delta-aminolevulinate synthase and cytochrome P-450 hemoproteins in hepatocyte culture. Effect of glucose and hormones. J Biol Chem. 1981;256:11182–90.
Jochems C, Fantini M, Fernando RI, Kwilas AR, Donahue RN, Lepone LM, et al. The IDO1 selective inhibitor epacadostat enhances dendritic cell immunogenicity and lytic ability of tumor antigen-specific T cells. Oncotarget. 2016;7:37762–72.
Mezrich JD, Fechner JH, Zhang X, Johnson BP, Burlingham WJ, Bradfield CA. An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J Immunol. 2010;185:3190–8.
Moyer BJ, Rojas IY, Murray IA, Lee S, Hazlett HF, Perdew GH, et al. Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors activate the aryl hydrocarbon receptor. Toxicol Appl Pharmacol. 2017;323:74–80.
Lewis HC, Chinnadurai R, Bosinger SE, Galipeau J. The IDO inhibitor 1-methyl tryptophan activates the aryl hydrocarbon receptor response in mesenchymal stromal cells. Oncotarget. 2017;8:91914–27.
A study to test combination treatments in people with advanced renal cell carcinoma (FRACTION-RCC).
A study to test combination treatments in patients with advanced gastric cancer (FRACTION-GC).
Liu XQ, Lu K, Feng LL, Ding M, Gao JM, Ge XL, et al. Up-regulated expression of indoleamine 2,3-dioxygenase 1 in non-Hodgkin lymphoma correlates with increased regulatory T-cell infiltration. Leuk Lymphoma. 2014;55:405–14.
Ott PA, Hodi FS, Kaufman HL, Wigginton JM, Wolchok JD. Combination immunotherapy: a road map. J Immunother Cancer. 2017;5:16.
Choueiri TK, Fishman MN, Escudier BJ, Kim JJ, Kluger HM, Stadler WM, et al. Immunomodulatory activity of nivolumab in previously treated and untreated metastatic renal cell carcinoma (mRCC): biomarker-based results from a randomized clinical trial. J Clin Oncol. 2014;32.
Urba WJ, Martín-Algarra S, Callahan M, Wolchok JD, Sharfman WH, Sosman JA, et al. Immunomodulatory activity of nivolumab monotherapy in patients with advanced melanoma (abstr). Presented at the Proceedings of the AACR 106th Annual Meeting 2015. 2015;75.
Liu X, Shin N, Koblish HK, Yang G, Wang Q, Wang K, et al. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood. 2010;115:3520–30.
Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol. 2015;33:1974–82.
A phase 3 study of pembrolizumab + epacadostat or placebo in subjects with unresectable or metastatic melanoma (Keynote-252/ECHO-301).
An adaptive study to match patients with solid tumors to various immunotherapy combinations based upon a broad biomarker assessment (ADVISE).