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Clinical Cancer Drugs


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

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


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
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.
[ ] [PMID: 20635308]
Saunders PR. In: Herbs Everyday Reference for Health Professionals. Canadian Pharmacists Association and Canadian Medical Association 2000; pp. 181-4.
Reishi Mushroom Ganoderma lucidum. American Herbal Pharmacopoeia and Therapeutic Compendium 2000.
Bensky D, Gamble A. Dan ShenChinese Herbal Medicine Materia Medica. Eastland Press 1993; pp. 267-8.
Bensky D, Gamble A. Ban Zhi LianChinese Herbal Medicine Materia Medica. Eastland Press 1993; p. 102.
McGuffin M, Kartesz JT, Leung AY, Tucker AO. Herbs of Commerce. 2nd ed. American Herbal Products Association 2000.
Ganoderma. In:Pharmacopoeia of the People’s Republic of China (English Edition 2000) 2000; 1: 93.
Chang R. effective dose of ganoderma in humans. proceedings of contributed symposium 59 A,B 5th International Mycological Congress Vancouver. 117-21.
Jin X, Ruiz Beguerie J, Sze DM, Chan GC. Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Database Syst Rev 2012; 6(6)CD007731
[] [PMID: 22696372]
Radix Salviae Miltiorrhizae. In: Pharmacopoeia of the People’s Republic of China (English Edition 2000). Chemical Industry Press 2000; 1: pp. 192-3.
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.
[] [PMID: 16291709]
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.
[ ] [PMID: 15325848]
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.
[] [PMID: 16450292]
Waterhouse DN. A novel combination of Chinese medicines to treat advanced cancers and lymphomas in rats. Chin Med 2009; 4: 22.
[ ] [PMID: 19943929]
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
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.
[] [PMID: 24388358]
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.
[] [PMID: 29381682]
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.
[] [PMID: 29441566]
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.
[] [PMID: 19097774]
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.
[] [PMID: 20382756]
Jia M, Souchelnytstkyi S. Comments on the cross-talk of TGFβ and EGF in cancer. Exp Oncol 2011; 33(3): 170-3.
[PMID: 21956473]
Derynck R, Akhurst RJ. Differentiation plasticity regulated by TGF-beta family proteins in development and disease. Nat Cell Biol 2007; 9(9): 1000-4.
[] [PMID: 17762890]
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.
[ ] [PMID: 26283373]
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]
Nacif M, Shaker O. Targeting transforming growth factor β (TGFβ) in cancer and non-neoplastic diseases. J Cancer Ther 2014; 5(7): 735-47.

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