A Randomized Double-Blind Phase 2 Study of Ruxolitinib (rux) or Placebo (pbo) with Capecitabine (cape) As Second-Line Therapy in Patients (pts) with Metastatic Pancreatic Cancer (Mpc).

4000 Background: Local and systemic inflammation (INFL) are hallmarks of cancer, including PC, that adversely impact prognosis. Given the role of JAK-STAT signaling in cancer INFL, the efficacy and safety of RUX, a JAK1/JAK2 inhibitor, given with CAPE in pts with mPC refractory to initial therapy was explored. Methods: Pts with adequate performance status and organ function who progressed after gemcitabine treatment were included. RUX + CAPE was well tolerated in a 9 pt safety run-in. Subsequently, 127 pts were randomized to CAPE 1000 mg/m2 BID days 1–14 with either RUX 15 mg BID or PBO on days 1–21 of a 21-day cycle. The primary endpoint was OS; secondary endpoints included PFS and ORR. To detect a HR ≤0.6 with 2-sided α=0.2 and β<0.2, final analysis was planned to occur after 97 deaths. Subgroup analyses were prespecified to explore treatment heterogeneity and a hypothesis that RUX would preferentially benefit pts with evidence of INFL. Results: In the randomized population, OS and PFS favored RUX (Tabl...