4O - Phase 1 study of E7046, a PGE2 receptor EP-4 inhibitor that targets immunosuppressive myeloid cells in the tumor microenvironment (TME) (4O)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Proffered Paper session
Topics Colon Cancer
Rectal Cancer
Gastrointestinal Cancers
Translational Research
Presenter Aparna Parikh
Citation Annals of Oncology (2017) 28 (suppl_11): xi1-xi2. 10.1093/annonc/mdx712
Authors D. Hong1, A. Varga2, A. Parikh3, G. Shapiro4, L. Reyderman5, M. Ren5, S. Dayal6, T. Binder5, C.E. Ooi5, Ö. Ataman6, A. Marabelle2
  • 1Department Of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 2Drug Development Department (ditep), Gustave Roussy, Villejuif/FR
  • 3Department Of Hematology/oncology And Medicine, Massachusetts General Hospital, Boston/US
  • 4Department Of Medicine, Harvard Medical School, Boston/US
  • 5Eisai, Inc., NJ 07677 - Woodcliff Lake/US
  • 6Eisai, Ltd., Hatfield/GB



E7046 is a selective small molecule antagonist of the prostaglandin E2 receptor-type-4 that inhibits the differentiation of monocytic myeloid lineage cells towards a pro-tumorigenic phenotype in the TME. This is a first-in-human study of single agent E7046.


Key eligibility criteria: patients (pts) ≥18 years with selected advanced cancers with high levels of myeloid infiltrate. The dose-escalation phase consisted of 6-pt cohorts of 125, 250, 500, and 750 mg (once-daily, oral, 21-day cycle) doses of E7046. Primary objectives were safety/tolerability, maximum tolerated dose (MTD) and/or RP2D. Secondary objectives included PK and initial anti-tumor activity; exploratory objectives included PD assessments on immune cells in tumor infiltrate and in peripheral blood and metabolic response by 18FDG-PET.


30 pts received E7046 (median age 58 yrs [24-78]; 2-7 lines of prior therapy). Most common tumor types were colorectal cancer (40%), pancreatic cancer (20%), and SCCHN (13%). No DLTs were observed and the MTD was not reached. The most frequent drug-related adverse events (AEs) were diarrhea (20%), decreased appetite, fatigue and nausea (13% each). Drug-related AEs of Gr 3/4 occurred in 4 pts (diarrhea, anaphylactic reaction, hypersensitivity, hyperuricemia, rash, generalized rash). 2 pts had drug-related serious AEs (rash, allergic reaction, fever in 1 pt; hyperuricemia, acute renal failure [Gr 2] in 1 pt). 3 pts discontinued treatment due to AEs (bowel obstruction, allergic reaction, abdominal pain). There were no drug-related deaths. E7046 exposure was dose proportional up to 500 mg with no incremental increase in exposure at 750 mg. E7046 was extensively metabolized, elimination half-life was ∼12hr and accumulation on multiple dosing was ∼2-fold. 2 pts are ongoing and preliminary efficacy showed no objective responses, 4 pts with durable SD or clinically stable (>4 mo) and 4 pts with 18FDG-PET metabolic responses.


Single-agent E7046 was tolerated with no MTD reached in heavily pretreated pts with myeloid-rich tumors. PD analysis of immune cell modulation to help determine the RP2D will be presented at the meeting.

Clinical trial identification


Legal entity responsible for the study

Eisai Inc.


Eisai Inc.


D. Hong: Research/Grant Funding: Bayer, Lilly, Genentech, LOXO, Pfizer, Amgen, Mirati, Ignyta, Merck, Daichi-Sanko, Eisai; Travel, accommodations, expenses: MiRNA, LOXO; Consulting or Advisory Role: Bayer, Baxter, Guidepoint Global; Other ownership interests: Oncoreseponse (founder). A. Parikh: Personal fees from Roche, outside the submitted work. G. Shapiro: Consulting: Pfizer, Lilly, G1 Therapeutics, Vertex, Roche; Research funding: Lilly. L. Reyderman, M. Ren, T. Binder, C.E. Ooi: Employee of Eisai Inc. S. Dayal: Employee of Eisai Ltd. Ö. Ataman: Former employee of Eisai Ltd. at time of study. A. Marabelle: Received clinical trial funding from Eisai; Received consulting fees from Eisai and Roche; Received funding for anti-CSF1R clinical trial from Roche. All other authors have declared no conflicts of interest.