Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session

2138 - Phase Ib study of PF-04136309 (an oral CCR2 inhibitor) in combination with nab-paclitaxel/gemcitabine in first-line treatment of metastatic pancreatic adenocarcinoma


09 Sep 2017


Poster display session


Cytotoxic Therapy;  Clinical Research;  Pancreatic Cancer


Marcus Noel


Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369


M. Noel1, M. Lowery2, D. Ryan3, B. Wolpin4, A. Bullock5, C. Britten6, B. Jin7, B.J. Ganguly8, C.T. Taylor9, D. Yin9, D.A. Wunderlich10, E.C. Gamelin9, D.C. Linehan1

Author affiliations

  • 1 School Of Medicine & Dentistry, University of Rochester Medical Center, 14642 - Rochester/US
  • 2 Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 3 Mgh Cancer Center, Massachusetts General Hospital, 02215 - Boston/US
  • 4 Dana-farber Cancer Institute, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 5 Division Of Hematology-oncology, Beth Israel Deaconess Medical Center, 02215 - Boston/US
  • 6 Hollings Cancer Center, Medical University of South Carolina, 29425 - Charleston/US
  • 7 Biostatistics, Pfizer, Cambridge/US
  • 8 Early Oncology Development And Clinical Research, Pfizer Inc, South San Francisco/US
  • 9 Early Oncology Development And Clinical Research, Pfizer Inc - USA, 92121 - San Diego/US
  • 10 Early Oncology Development And Clinical Researchworldwide Research And Development, Pfizer Inc, Groton/US


Abstract 2138


CCL2/CCR2 plays a key role in immunosuppressive properties of the pancreatic adenocarcinoma tumor microenvironment (TME), patients’ (pts) prognosis and chemoresistance. PF-04136309 (oral CCR2 inhibitor) blocks recruitment and migration of inflammatory monocytes (IM) from bone marrow (BM) to TME.


This ongoing multicentre phase Ib study is investigating PF-04136309 in combination with nab-paclitaxel and gemcitabine (nab-P+Gem) in pts with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC). Objectives; primary: safety, tolerability, maximum tolerated dose, recommended dose; secondary: pharmacokinetics (PK), pharmacodynamics of PF-04136309; exploratory: efficacy, proof of mechanism (POM), as CCR2 inhibition trapped IMs in BM and decreased IMs in peripheral blood and metastatic tumor tissue with paired tumor biopsies and bone marrow aspirates at baseline and after 1 or 2 cycles.


From May 1, 2016–March 17, 2017, 21 pts (ECOG PS 0-1; mean age 61.8 yrs; range 46-79) received PF-04136309. Cohort 1, starting dose level: 1 grade 3 drug-related DLT (cognitive disorder), 1 grade 2 and 2 grade 1 rashes. Cohort 2 (1 dose level reduction): 4 (23.5%) grade 3 drug-related DLT (1 scalp dysesthesia, 1 ALT-AST, 1 pneumonia, 1 pneumonitis). Recommended total daily dose 1000mg. With median duration of treatment of 4 mo (1–9), grade ≥3 drug-related AEs: neutropenia 3 (17.6%), fatigue 4 (23.5%), diarrhea 1 (5.9%), lung toxicities 3 (17.6%); % pts with dose-reduction: nab-P 47%, Gem 53%, PF-04136309 41%; median relative dose intensity: nab-P 84%, Gem 67%, PF-04136309 80%. Early objective response in 10 evaluable pts: PR 6 (60%), SD 1 (10%), PD 3 (30%). Disease control rate at 4 mo: 70%. Median PFS not reached (8 pts on treatment). PF-04136309 PK was consistent with previous single agent studies. Almost all had a drop in peripheral blood CD14+CCR2+ monocytes (baseline-Day 15). IMs decreased and CD4+ and CD8+ T cells increased (5–8 fold) in paired biopsy samples. One of 2 pts had increased tumor associated PD1+CD4+ and PD-1+CD8+ T cells.


Encouraging safety, favorable PK, clinical responses and POM with CCR2 inhibition plus nab-P+Gem in mPDAC pts.

Clinical trial identification


Legal entity responsible for the study

Pfizer Inc.


Pfizer Inc.


M. Noel: Speaker’s bureau for Taiho Oncology. M. Lowery: Advisory board: Agios Pharmaceuticals, Celgene. D. Ryan: MPM Capital. C. Britten: Research paid to institution: Pfizer. B. Jin, C.T. Taylor, B.J. Ganguly, D. Yin, E.C. Gamelin, D.A. Wunderlich: Employee and stockholder of Pfizer Inc. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.