A phase I/II study of RX-3117, an oral antimetabolite nucleoside, in combination with nab-paclitaxel (nab-pac) as first-line treatment of metastatic pancreatic cancer (met-PC): Preliminary results.

420 Background: RX-3117 is an oral small molecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by cancer-enriched uridine cytidine kinase 2. Single agent RX-3117 has demonstrated efficacy in a phase III single agent clinical study of RX-3117 in met-PC and bladder cancer. RX-3117 in combination with nab-pac is being evaluated as first line treatment of met-PC cancer. Methods: This is a multicenter, open label phase I/II study (NCT03189914). Eligible subjects (aged ≥ 18 years) have histologically or radiologically proven met-PC with no prior therapies for metastatic disease, ECOG PS 0-1, and normal lab values. phase I identified the MTD dose that is being further evaluated in the phase II: RX-3117 (700 mg administered orally once-daily for 5 consecutive days with 2 days off per week) and nab-pac (125 mg/m 2 administered once weekly) for 3 weeks with 1 week off per 4-week cycle. The Safety Committee reviewed data from phase I before moving to phase II. The primary endpoint of phase II (dose expansion) is an adequate number of responders based on PFS at 4 months and/or objective clinical response per RECIST v1.1. Results: As of September 21, 2018, 8 phase I subjects and 13 phase II subjects were enrolled and treated (9 males and 12 females, median age 67 years). The most common (≥ 15%) related adverse events were nausea, diarrhea, fatigue, alopecia, decreased appetite, rash, vomiting, and anemia. Fourteen subjects had at least one on-study scan (after 2 cycles). One subject experienced a complete response (CR) after 6 cycles of therapy with normalization of CA19.9 (-76%). Three subjects exhibited a partial response (PR): two after 2 cycles (39-47%) and one after 4 cycles of therapy (36%). Eight subjects had stable disease for at least 2 months, and 4 subjects had PFS of at least 4 months. The disease control rate (CR+PR+SD) was 86% in evaluable subjects while the overall response rate (CR+PR) was 29%. Conclusions: RX-3117 in combination with nab-pac appears to be safe and well tolerated in subjects with met-PC. Antitumor activity per RECIST was observed in 12 subjects. Phase II of the clinical study is currently ongoing. Clinical trial information: NCT03189914.