Background: RX-3117 is an oral smallmolecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by uridine cytidine kinase 2. RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. Data from stage 1 of the Phase 1b/2a clinical study of RX3117 as a single agent in subjects with metastatic pancreatic cancer is described below. Methods: Stage 1 of the Phase 1b/2a study (NCT02030067) is designed to evaluate safety, tolerability and efficacy following treatment with 700 mg administered orally once-daily for 5 consecutive days with 2 days off per week for 3 weeks with 1 week off in each 4 week cycle in a 2-stage Simon design. Eligible subjects (aged ≥ 18 years) were those with relapsed/refractory metastatic pancreatic cancer. The primary endpoint is a ≥ 20% (2 out of 10 subjects) rate of progression free survival (PFS) benefit (i.e., proportion of subjects with stable disease for at least 4 months) and/or a 10% (1 of 10 subjects) with a partial response rate or better. Results: As of Sep 2016, 8 out of 10 subjects have been enrolled (4 females, 4 males), the mean age was 70 years, ECOG performance status was 1 and 5 subjects had received more than 4 prior therapies. Two subjects met the primary endpoint of stable disease with a duration of 140-168 days at the time of this submission. The most frequent adverse events were moderate to severe anemia, mild to moderate fatigue, abdominal pain and diarrhea. Conclusions: This ongoing trial shows an early efficacy signal where RX-3117 is active against advanced pancreatic cancer. As the primary endpoint has been achieved, the study will now move to stage 2 where an additional 40 subjects with advanced pancreatic cancer will be enrolled. Clinical trial information: NCT02030067