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 Cytotoxic agents
Clinical research
Basic Scientific Principles
Biological therapy
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.