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Clinical Cancer Drugs

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ISSN (Print): 2212-697X
ISSN (Online): 2212-6988

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Clinical Trial

A Phase I Study of OMN54 (Aneustat™) in Patients with Advanced Malignancies

Author(s): Karen A. Gelmon*, Christian Kollmannsberger, Stephen Chia, Anna V. Tinker, Teresa Mitchell, Stephen Lam, Teresa Joshi, David Kwok, John Ostrem, Simon Sutcliffe and Daniel J. Renouf

Volume 7, Issue 2, 2020

Page: [125 - 132] Pages: 8

DOI: 10.2174/1574893615999200601130946

open access plus

Abstract

Background/Objective: With the increasing interest in natural products, a phase I openlabel study of OMN54 (Aneustat™) in patients with advanced malignancies was initiated to determine toxicity, maximum tolerated dose (MTD), dose limiting toxicities (DLT), and pharmacokinetics (PK). OMN54 is a multitargeted agent, combining three Chinese botanicals; Ganoderma lucidium, Salvia miltiorrhiza and Scutellaria barbata.

Methods: Eligible patients (pts) were >18 years of age with advanced solid tumors, able to swallow oral capsules, ECOG performance status < 2, measurable disease as defined by RECIST 1.1 and adequate organ function.

Results: Twenty-two patients were enrolled in 6 dose levels, 2 with daily dosing and 4 with twicedaily dosing ranging from 1 to 5 grams daily. All were evaluated for toxicity and 20 for response. No treatment-related dose-limiting toxicities (DLTs) were reported and the recommended phase II dose (RP2D) was determined to be 2.5 g twice daily. Seven adverse events in 5 patients were reported as possibly drug-related; 6 were GI toxicity and 1 was a skin disorder. All were grade 1 except one grade 2 vomiting. No RECIST responses were seen. Six pts were treated with > 2 cycles; one for 8 cycles. Four patients had reductions in TGF –β and EGF, exploratory biomarkers possibly suggestive of a drug effect. Plasma half-lives of 1 -2 hours were noted for all parent drug chemical markers with no accumulation over time.

Conclusion: OMN54 was well tolerated, with no DLTs observed. Further studies at the RP2D will assess the biological activity.

Keywords: Phase 1, natural products, advanced cancer, OMN54, maximum tolerated dose (MTD), dose limiting toxicities (DLT).

Graphical Abstract

[1]
Hsiao WL, Liu L. The role of traditional Chinese herbal medicines in cancer therapy--from TCM theory to mechanistic insights. Planta Med 2010; 76(11): 1118-31.
[http://dx.doi.org/10.1055/s-0030-1250186 ] [PMID: 20635308]
[2]
Saunders PR. In: Herbs Everyday Reference for Health Professionals. Canadian Pharmacists Association and Canadian Medical Association 2000; pp. 181-4.
[3]
Reishi Mushroom Ganoderma lucidum. American Herbal Pharmacopoeia and Therapeutic Compendium 2000.
[4]
Bensky D, Gamble A. Dan ShenChinese Herbal Medicine Materia Medica. Eastland Press 1993; pp. 267-8.
[5]
Bensky D, Gamble A. Ban Zhi LianChinese Herbal Medicine Materia Medica. Eastland Press 1993; p. 102.
[6]
McGuffin M, Kartesz JT, Leung AY, Tucker AO. Herbs of Commerce. 2nd ed. American Herbal Products Association 2000.
[7]
Ganoderma. In:Pharmacopoeia of the People’s Republic of China (English Edition 2000) 2000; 1: 93.
[8]
Chang R. effective dose of ganoderma in humans. proceedings of contributed symposium 59 A,B 5th International Mycological Congress Vancouver. 117-21.
[9]
Jin X, Ruiz Beguerie J, Sze DM, Chan GC. Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Database Syst Rev 2012; 6(6)CD007731
[http://dx.doi.org/10.1002/14651858.CD007731.pub2] [PMID: 22696372]
[10]
Radix Salviae Miltiorrhizae. In: Pharmacopoeia of the People’s Republic of China (English Edition 2000). Chemical Industry Press 2000; 1: pp. 192-3.
[11]
Zhou L, Zuo Z, Chow MS. Danshen: An overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. J Clin Pharmacol 2005; 45(12): 1345-59.
[http://dx.doi.org/10.1177/0091270005282630] [PMID: 16291709]
[12]
Yin X, Zhou J, Jie C, Xing D, Zhang Y. Anticancer activity and mechanism of Scutellaria barbata extract on human lung cancer cell line A549. Life Sci 2004; 75(18): 2233-44.
[http://dx.doi.org/10.1016/j.lfs.2004.05.015 ] [PMID: 15325848]
[13]
Chan JY, Tang PM, Hon PM, et al. Pheophorbide a, a major antitumor component purified from Scutellaria barbata, induces apoptosis in human hepatocellular carcinoma cells. Planta Med 2006; 72(1): 28-33.
[http://dx.doi.org/10.1055/s-2005-873149] [PMID: 16450292]
[14]
Waterhouse DN. A novel combination of Chinese medicines to treat advanced cancers and lymphomas in rats. Chin Med 2009; 4: 22.
[http://dx.doi.org/10.1186/1749-8546-4-22 ] [PMID: 19943929]
[15]
Mikovits J, Gerwick L, Oroudjev E, et al. OMN54 a multifunctional, multitargeted (MFMT) agent with potent effects on the inflammatory process associated with cancer initiation and progression. Abstract AACR 2008
[16]
Qu S, Wang K, Xue H, et al. Enhanced anticancer activity of a combination of docetaxel and Aneustat (OMN54) in a patientderived, advanced prostate cancer tissue xenograft model. Mol Oncol 2014; 8(2): 311-22. www.sciencedirect.com
[http://dx.doi.org/10.1016/j.molonc.2013.12.004] [PMID: 24388358]
[17]
Qu S, Ci X, Xue H, et al. Treatment with docetaxel in combination with Aneustat leads to potent inhibition of metastasis in a patient-derived xenograft model of advanced prostate cancer. Br J Cancer 2018; 118(6): 802-12.
[http://dx.doi.org/10.1038/bjc.2017.474] [PMID: 29381682]
[18]
Qu S, Xue H, Dong X, et al. Aneustat (OMN54) has aerobic glycolysis-inhibitory activity and also immunomodulatory activity as indicated by a first-generation PDX prostate cancer model. Int J Cancer 2018; 143(2): 419-29.
[http://dx.doi.org/10.1002/ijc.31310] [PMID: 29441566]
[19]
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45(2): 228-47.
[http://dx.doi.org/10.1016/j.ejca.2008.10.026] [PMID: 19097774]
[20]
Wang Q, Hao H, Zhu X, et al. Regioselective glucuronidation of tanshinone iia after quinone reduction: identification of human UDP-glucuronosyltransferases, species differences, and interaction potential. Drug Metab Dispos 2010; 38(7): 1132-40.
[http://dx.doi.org/10.1124/dmd.109.031864] [PMID: 20382756]
[21]
Jia M, Souchelnytstkyi S. Comments on the cross-talk of TGFβ and EGF in cancer. Exp Oncol 2011; 33(3): 170-3.
[PMID: 21956473]
[22]
Derynck R, Akhurst RJ. Differentiation plasticity regulated by TGF-beta family proteins in development and disease. Nat Cell Biol 2007; 9(9): 1000-4.
[http://dx.doi.org/10.1038/ncb434] [PMID: 17762890]
[23]
Ma C, Zhang N. Transforming growth factor-β signaling is constantly shaping memory T-cell population. Proc Natl Acad Sci USA 2015; 112(35): 11013-7.
[http://dx.doi.org/10.1073/pnas.1510119112 ] [PMID: 26283373]
[24]
Wei T, Zhang J, Qin Y, et al. Increased expression of immunosuppressive molecules on intratumoral and circulating regulatory T cells in non-small-cell lung cancer patients. Am J Cancer Res 2015; 5(7): 2190-201.
[PMID: 26328249]
[25]
Nacif M, Shaker O. Targeting transforming growth factor β (TGFβ) in cancer and non-neoplastic diseases. J Cancer Ther 2014; 5(7): 735-47.
[http://dx.doi.org/10.4236/jct.2014.57082]

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