KPT-9274, a potentially first-in-class, dual NAMPT/PAK4 inhibitor, has shown single-agent anticancer activity in hematologic and solid tumor cell lines and xenografts. KPT-9274 has shown anti-tumor activity in combination with nivolumab in nonclinical models. KCP-9274-901 was a first-in-human, multi-center, open-label clinical study to assess preliminary safety, tolerability, and efficacy of KPT-9274 in patients with advanced solid tumors. This study was conducted in three parts. A two-part (A, B) dose escalation phase to determine the recommended phase II dose and maximum tolerated dose (MTD) of KPT-9274 alone and with niacin. Part 3 (C) was a dose-finding and expansion phase in patients with melanoma treated with KPT-9274 plus nivolumab. A total of 60 patients were enrolled (part A and B n = 50; part C n = 10). Three dose-limiting toxicities (DLTs) were observed in the 40-mg (n = 1) and 80-mg plus niacin (n = 2) cohorts. MTD was not reached in parts A and B and was 60 mg plus nivolumab in part C. The most frequently reported TEAEs (≥30%) were anemia (82.6%), arthralgia (52.2%), and fatigue (43.5%). Patient enrollment was halted prematurely due to a lack of observable efficacy in all parts of the study. The MTD of KPT-9274 was not reached in a dose escalation study conducted in patients with advanced solid tumors. Clinical activity was not observed at study doses in combination with niacin or nivolumab. Further investigation into potential therapeutic areas where KPT-9274 may serve as a targeted agent is warranted. Clinical trial registration: www.clinicaltrials.gov , NCT02702492.
Razak et al. (Fri,) studied this question.