413P - RX-3117, a novel Hypomethylating agent, shows promising therapeutic activity in combination with nab-paclitaxel and check-point inhibitors in precl...

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
Drug Development
Cancer Immunology and Immunotherapy
Presenter Julie Frank
Citation Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367
Authors J. Frank1, Y.B. Lee1, D.J. Kim1, E. Benaim2
  • 1Research, Rexahn Pharmaceuticals, 20850 - Rockville/US
  • 2Clinical Trial, Rexahn Pharmaceuticals, 20850 - Rockville/US



A novel nucleoside analogue, RX-3117, is being evaluated in a Phase IIa study in patients with advanced pancreatic and bladder cancer. RX-3117 shows promising antitumor activity in xenografts including patient-derived xenografts resistant to gemcitabine. Here we demonstrate the preclinical effects of combination therapy with RX-3117 + Abraxane or anti-PD1 immunotherapy.


One colorectal (MC38), pancreatic (Pan02) syngeneic xenograft and patient-derived pancreatic (CTG-0723) xenograft model were exposed to 60 mg/kg RX-3117 po, 5 days on, 2 days off for three weeks. Pan02 and MC38 received RX-3117 alone or in combination with 100ug anti-PD1, ip. PDx CTG-0723 received one cycle of RX-3117, followed by a second cycle of RX-3117 + 10 mg/kg Abraxane, iv. MC38 tumor-infiltrating lymphocytes were measured at days 5 and 12 with RX-3117.


In MC38 at day 28, RX-3117 or anti-PD1 showed TGIs of 90% and 93%, whereas the combination showed 99% TGI. Differences were also observed in TILs. Relative to vehicle (CD4+:10.6+/-1.6, CD8+: 8.6+/-1.1), %CD4 + (17.4+/-1.4) and CD8+ cells (12.3+/-1) increased. %MDSCs decreased on Day 5 in blood (42+/-7.7 vs 29+/-6). %CD8+ increased (9.6+/-3.3 vs 12.3+/-3.2) and %MDSC decreased (15.4 +/- 3.7 vs 10.6 +/- 3.3) in tumor on Day 12. In Pan02, RX-3117 + anti-PD1 resulted in a day 32 TGI of 60%. Anti-PD1 alone had a day 32 28% TGI. In CTG-0723, the first cycle of RX-3117 at 10, 30 and 60 mg/kg produced TGIs of 33%, 46% and 77%. The second cycle, RX-3117 + Abraxane, day 46 TV showed TGIs of 55%, 58% and 83%.


We demonstrate the antitumor effect of RX-3117 as a single agent and in combination with Abraxane or anti-PD-1. The combination of RX-3117/anti-PD1 in MC38 produced 7 tumor-free survivors out of 10 compared to 2 of 10 by anti-PD1 alone, indicating RX-3117 may mobilize the right population of lymphocytes to enable anti-PD-1 to work more effectively. In Pan02, RX-3117 exhibited better TGI than anti-PD-1. In CTG-0723, the combination of RX-3117 and Abraxane showed additive TGI. These studies demonstrate the therapeutic potential of RX-3117 in multiple cancers and validate the combination of RX-3117 with anti-PD1 in several cancer types.

Clinical trial identification

Legal entity responsible for the study

Rexahn Pharmaceuticals, Inc.


Rexahn Pharmaceuticals, Inc


J. Frank, Y.B. Lee, D.J. Kim: Employee of Rexahn Pharmaceuticals. E. Benaim: Officer at Rexahn Pharmaceuticals, employee, stock-holder.