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Developmental therapeutics

3145 - Phase 1 Study of E7046, a PGE2 Receptor EP-4 Inhibitor That Targets Immunosuppressive Myeloid Cells in the Tumor Microenvironment


09 Sep 2017


Developmental therapeutics


Clinical Research


David Hong


Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367


D.S. Hong1, A. Varga2, A. Parikh3, G. Shapiro4, L. Reyderman5, M. Ren5, S. Dayal6, T. Binder7, C.E. Ooi7, O. Ataman6, A. Marabelle2

Author affiliations

  • 1 Division Of Cancer Medicine University Of Texas, The University of Texas M. D. Anderson Cancer Center, 77035 - Houston/US
  • 2 Drug Development, Gustave Roussy, Villejuif/FR
  • 3 Hematology/oncology And Medicine, Massachusetts General Hospital, Boston/US
  • 4 Dept. Of Medicine, Harvard Medical School, 02215 - Boston/US
  • 5 Eisai, Inc., Woodcliff Lake/US
  • 6 Eisai, Ltd., Hatfield/GB
  • 7 Eisai, Inc., NJ 07677 - Woodcliff Lake/US


Abstract 3145


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.S. Hong: Research/Grant Funding: Bayer, Lilly, Genentech, LOXO, Pfizer, Amgen, Mirati, Ignyta, Merck, Daichi-Sanko, Eisai. Travel/Accommodations: MiRNA, LOXO. Consulting/Advisory: Bayer, Baxter, Guidepoint Global. Other interests: Oncoreseponse (founder). L. Reyderman, M. Ren, T. Binder, C.E. Ooi, S. Dayal, O. Ataman: Employee of Eisai Ltd. A. Marabelle: Clinical trial funding from Eisai. Consulting fees from Eisai and Roche. Funding for anti-CSF1R clinical trial from Roche. All other authors have declared no conflicts of interest.

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