Abstract B30: A phase 1 open label, dose-escalation trial evaluating the safety and tolerability of EF-022, macrophage activator, in subjects with advanced solid malignancies
Authors: Golan Talia , Berger Raanan , Ackerstein Aliza , Raskin Steve , Lesokhin Alexander M. , Sidransky David , Levitt Mark L. , Gadassi Hana , Yogev Uri , Shahar Michal 
Published: May 2016

Abstract
Scientific background: Activated macrophages, present in excess during natural inflammatory responses, bear the potential to kill and eradicate cancer cells. Efranat has developed cancer immunotherapy based on macrophage activation using a plasma protein designated EF-022, a modified Vitamin D Binding Protein Macrophage Activator.
Methods: We performed an open label single-center phase I study in patients diagnosed with inoperable, recurrent or metastatic malignant solid tumors, deemed incurable, and who have failed to respond to standard therapy or for whom no standard therapy is available. The dose-escalation study was comprised of three cohorts, each receiving intramuscular (IM) injections of EF-022, once weekly for two cycles of treatment. Each cycle consisted of 4 weekly injections. Three dose levels were evaluated: 100 ng, 500ng and 1000ng. Patients were followed for up to 12 months from the start of treatment. The primary study objectives were to determine the safety and tolerability and to define the dose-limiting toxicities (DLT) and maximum tolerated doses (MTD). Blood and tissue biopsies were obtained for pharmacodynamics evaluation.
Results: 12 patients with solid tumors have been enrolled. Median age = 65; male: female = 5:7. Among 12 treated patients, the most frequent drug related adverse events were flu like symptoms and rash and were mostly grade 1 or 2; no serious adverse events (SAE) related to study drug were observed. No DLTs were observed. CT imaging performed at 8 weeks showed stable disease (SD) in 5/12 patients (cholangiocarcinoma, H&N cancer, esophageal-gastric cancer, ovarian cancer and liposarcoma). 11 patients completed 57 days of treatment and 1 patient left the study after 1st cycle of treatment (29 days). Significant reduction in Tregs (CD4+CD127-CD25+) levels and increase in M1/M2 monocyte (CD14+HLA+ /CD16+CD163+) ratio in the blood was detected in most of the patients. In patients demonstrating SD an increase in the M1/M2 macrophage ratio (CD68+CD163-/ CD68+CD163+) was found at the tumor site.
Conclusions: Treatment with EF-022 has an acceptable safety profile and resulted in disease stabilization in 42% of patients. Pharmacodynamics markers suggest a reduction of Tregs and increase of the M1/M2 ratio. These findings are being further explored in a dose expansion cohort.
ClinicalTrials.gov Identifier: NCT02052492
Citation Format: Talia Golan, Raanan Berger, Aliza Ackerstein, Steve Raskin, Alexander M. Lesokhin, David Sidransky, Mark L. Levitt, Hana Gadassi, Uri Yogev, Michal Shahar. A phase 1 open label, dose-escalation trial evaluating the safety and tolerability of EF-022, macrophage activator, in subjects with advanced solid 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 B30.