A phase 1b/2 study of INCB039110 + nab-paclitaxel (N) and gemcitabine (G) in patients (pts) with advanced solid tumors and pancreatic cancer (PC).

Abstract

362 Background: JAK-STAT activity has been associated with malignant cell proliferation and production of proinflammatory cytokines involved in cancer progression. INCB039110 is a potent and selective inhibitor of JAK1. Methods: This was a 2-part phase 1b/2 open-label study evaluating INCB039110 (300 or 400 mg QD) in combination with N and G in pts with advanced or metastatic solid tumors (Part 1 [P1], dose optimization phase) and pts with advanced or metastatic PC who had not received prior chemotherapy (Part 2 [P2] and 2A [P2A]). Pts in P2 received the MTD established in P1: INCB039110 (300 mg QD) + N (125 mg/m2 day [d] 1, 8, 15) + G (1000 mg/m2 d 1, 8, 15), 28-d cycle. For exploratory purposes, pts in P2A underwent a 7-d induction phase with INCB039110 (200 mg QD) before receiving INCB039110 (200 mg QD) + N (125 mg/m2 d 1, 8, 15) + G (1000 mg/m2d 1, 8, 15). The primary objective was to evaluate safety/tolerability. Results: 55 pts were enrolled (27 P1, 20 P2, and 8 P2A). Most patients had advanced PC (n = 46). Median age was 65 (P1), 67 (P2), and 66 years (P2A). Prior therapy: 67% in P1, 30% in P2, and 0% in P2A. The most common reasons for treatment discontinuation were adverse events (AEs; 41% P1, 20% P2, 38% P2A), disease progression (37% P1, 45% P2, 0% P2A), and study termination by the sponsor (0% P1, 0% P2, 38% P2A). Median treatment durations were 84 d (P1), 121 d (P2), and 47 d (P2A). The most common non-hematologic AEs (all grades) were fatigue (59% P1, 75% P2, 88% P2A), nausea (41% P1, 50% P2, 38% P2A), pyrexia (37% P1, 40% P2, 13% P2A), and peripheral edema (30% P1, 50% P2, 25% P2A), with few grade 3 or 4 non-hematologic AEs. The most common grade 3 or 4 hematologic AEs (laboratory values) were neutropenia (33% P1, 60% P2, 13% P2A), lymphopenia (30% P1, 30% P2, 13% P2A), and leukopenia (30% P1, 45% P2, 0% P2A). The most common serious AEs occurring in ≥ 3 pts were pneumonia (n = 4 P1, n = 2 P2, n = 0 P2A) and anemia (n = 3 P1, n = 2 P2, n = 2 P2A). Among evaluable patients, ORR (all PRs) and DCR were 27% (13/48) and 75% (36/48), respectively. Responses were seen across INCB039110 doses. Conclusions: INCB039110 + N/G showed an acceptable safety profile in pts with advanced PC, with the combination demonstrating clinical activity. Clinical trial information: NCT01858883.