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.