Xpovio: what was done before first-in-human, and what came after?

“Study treatment on Arm 1 during the dose escalation phase followed a standard 3+3 design with a starting dose of selinexor 3 mg/m2.”

“Study title/ number: A 13-Week (13-Cycle) Oral Gavage Toxicity and Toxicokinetic Study of KPT-330 in Sprague Dawley Rats with a 4-Week Recovery Period/ KNC-G-13-001”

“Thirteen-week repeat-dose oral toxicity and toxicokinetic studies were conducted in the rat (0, 0.25, 1, or 4 mg/kg selinexor; 5 total doses given every 2-week period) and monkey (0, 0.1, 0.3, 1 mg/kg selinexor; 2 to 3 times/week) to support the NDA.”

“No carcinogenicity study was conducted, and only maternal and embryo-foetal development toxicity were carried out, indicating a NOAEL value at 0.25 mg/Kg/day for rats. No data for a second species were provided.”

“Adverse developmental outcomes occurred at ≥ 0.75 mg/kg/day and included alterations to growth (e.g., fetal weights in the 0.75 and 2 mg/kg/day groups were 13.5% and 32.4% lower than controls) and structural abnormalities (such as incomplete or delayed ossification of sternebra(e) and/or vertebral arches, and/or unossified and bent ribs).”

“No carcinogenicity study was conducted, and only maternal and embryo-foetal development toxicity were carried out, indicating a NOAEL value at 0.25 mg/Kg/day for rats.”

“Carcinogenicity studies were not conducted to support the use of selinexor for the proposed indication.”

“Carcinogenicity studies were not conducted to support the use of selinexor for the proposed indication.”

“Carcinogenicity studies were not conducted to support the use of selinexor for the proposed indication.”