A phase 1b study of ruxolitinib (Rux) + gemcitabine (G) ± nab-paclitaxel (N) in patients (pts) with advanced solid tumors.

Abstract

439 Background: Aberrant activation of the JAK-STAT pathway has been associated with increased malignant cell proliferation and survival. Rux, a potent JAK1/2 inhibitor, was evaluated in combination with G±N in advanced solid tumors. Methods: This was an open-label study of Rux + G, without N (regimen A) or with N (regimen B) in advanced solid tumors. The objective of the dose-finding phase (reported here) was to identify MTDs of Rux + G and Rux + G/N. See Table for evaluated cohorts. Results: Among 42 pts enrolled, median age was 62.5 years, 81% had pancreatic cancer (PC), 50% had 1 prior regimen and 12% had 2 prior regimens. Discontinuations were mainly due to radiological or clinical disease progression (86% of pts). Median treatment durations: 55.5 d (A) and 97.5 d (B). 4 pts in B had DLTs: Grade (Gr) 3 pneumonia (n = 1, SAE), Gr 3 neutropenia (n = 1) and Gr 4 thrombocytopenia (n = 2). Table summarizes AEs. The most common Gr 3/4 hem AEs (lab) were anemia (88% A, 85% B) and thrombocytopenia (81% A, 89% B). SAEs occurring in ≥ 2 pts were abdominal pain (n = 4, A), sepsis (n = 2, A), dehydration, anemia and asthenia (n = 2 each, B). Rux + G was tolerated with standard doses of G. Rux + G/N was tolerated with reduced doses of G/N or concomitant GCSF. These combinations were not pursued further, therefore MTDs were not defined. ORRs were 2/16 (13%) in A and 10/26 (39%) in B. ORRs in PC pts: 8/34 (24%); 2/14 (14%) in A and 6/20 (30%) in B. Conclusions: Rux + G or Rux + G/N at the doses investigated were generally safe and well tolerated in pts with advanced PC and other solid tumors. ORRs were noted in multiple tumor types including PC. Clinical trial information: NCT01822756. [Table: see text]