Abstract C41: A phase 1 study of OMN54 in patients with advanced malignancies

Abstract

Purpose: With the increasing interest in natural products as therapeutics, we performed a Phase I open label study of OMN54 in patients with advanced malignancies to determine toxicity, maximum tolerated dose (MTD), dose limiting toxicities (DLT), and pharmacokinetics (PK). OMN54 is a multitargeted agent prepared from three Chinese botanical sources: Ganoderma lucidum, Salvia miltiorrhiza, and Scutellaria barbata, each with long histories of use as single agents. Methods: Eligible patients (pts) were ≥ 18 years with advanced solid tumor malignancies, able to swallow oral capsules, ECOG performance status ≤ 2, measurable disease as defined by RECIST 1.0, and adequate organ function. Results: 22 pts were enrolled in 6 dose levels, 2 at daily and 4 with twice daily dosing ranging from 1 to 5 gm orally per day; all evaluable for toxicity and 20 for response. Most common cancers included colorectal (13 pts), non small cell lung (3 pts), and ovarian (2 pts). 5 pts patients completed Cycle 1, 9 pts Cycle 2, 3 pts Cycle 3 and 1 pt each completed Cycles 4, 5, and 8. 2 pt had < 1 cycle. Only 7 AEs in 5 pts were reported as possibly related to study drug; 6 were gastrointestinal disorders, 1 a skin disorder. One GR 2 AE of vomiting was probably related to study drug. All other AEs were Grade 1. There were no treatment-related SAEs or DLTs. A recommended phase II dose (RP2D) is 2.5 g orally twice daily. PK data revealed evidence of detectable plasma total OMN54 in cohorts 1 to 6 with all 4 parent drug chemical markers with plasma half-lives of 1- 2 hours and no evidence of accumulation. Preliminary evidence of biological activity was seen with stable disease for 8 months in 1 pt and 4 pts with dose responsive reductions in TGF-β, EGF & Rantes, biomarkers of immune suppression. Significant TGF-β decreases were seen for 4 pts at doses of 2gm daily to 2.5 gm bid including an ovarian, colorectal, fallopian tube and esophageal cancer. Conclusion: OMN54 was well tolerated with no DLTs observed. Further studies at RP2D of 2.5 g bid orally should be done to assess activity. Citation Format: Daniel Renouf, Christian Kollmannsberger, Kim Chi, Stephen Chia, Anna Tinker, Teresa Mitchell, Stephen Lam, Teresa Joshi, David Kwok, John Ostrem, Simon Sutcliffe, Karen A. Gelmon. A phase 1 study of OMN54 in patients with advanced malignancies. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C41.

Aneustat (OMN54) has aerobic glycolysis‐inhibitory activity and also immunomodulatory activity as indicated by a first‐generation PDX prostate cancer model

“…This suggestion is supported by the finding in the Aneustat Phase-I clinical trial that treatment with Aneustat led to a reduction in the levels of immune suppression markers in patients. 16 Further studies are needed to establish the mechanisms of action underlying the immunomodulatory activity of Aneustat. Restoration of the host anticancer immune response by Aneustat should be beneficial for potential clinical therapy of advanced prostate cancers using docetaxel combined with Aneustat, as previously reported.…”

“…Recently, a Phase-I Clinical Trial (NCTId: NCT01555242) has shown that Aneustat was well tolerated by patients. Furthermore, treatment with Aneustat led to a decrease in the levels of immune suppression markers in patients (e.g., TGF-b), 16 indicative of an Aneustat-induced reduction in cancer-induced immunosuppression. As well, preliminary preclinical studies have indicated that Aneustat has anti-inflammatory and immunomodulatory activities.…”

Natural compounds targeting glycolysis as promising therapeutics for gastric cancer: A review

“…Camptothecin analogs, mainly camptothecin and irinotecan, extracted from Camptotheca acuminate , are used in the treatment of multiple solid tumor types ( Mann, 2002 ). Aneustat (OMN54), a mixture of extracts of Ganoderma lucidum , Salvia miltiorrhiza and Scutellaria barbata , has shown favorable anticancer effect in a Phase-I Clinical Trial (NCTId: NCT01555242) ( Renouf et al, 2015 ). In vitro experiments showed that Aneustat effectively inhibited the aerobic glycolysis of LNCaP prostate cancer cells ( Qu et al, 2018 ).…”