Carcinogenicity studies have not been conducted with selinexor.
Selinexor was not mutagenic in vitro in a bacterial reverse mutation (Ames) assay and was not clastogenic in either the in vitro cytogenetic assay in human lymphocytes or in the in vivo rat micronucleus assay.
Fertility studies in animals have not been conducted with selinexor. In repeat-dose oral toxicity studies, selinexor was administered for up to 13 weeks in rats and monkeys. Reduced sperm, spermatids, and germ cells in epididymides and testes were observed in rats at ≥1 mg/kg, decreased ovarian follicles were observed in rats at ≥2 mg/kg, and single cell necrosis of testes was observed in monkeys at ≥1.5 mg/kg. These dose levels resulted in systemic exposures approximately 0.11, 0.28, and 0.53 times, respectively, the exposure (AUClast ) in humans at the recommended human dose of 80 mg.
The efficacy of XPOVIO plus dexamethasone was evaluated in STORM (KCP-330-012; NCT02336815). STORM was a multicenter, single-arm, open-label study of adults with relapsed or refractory multiple myeloma (RRMM). STORM Part 2 included 122 patients with RRMM who had previously received three or more anti-myeloma treatment regimens including an alkylating agent, glucocorticoids, bortezomib, carfilzomib, lenalidomide, pomalidomide, and an anti-CD38 monoclonal antibody; and whose myeloma was documented to be refractory to glucocorticoids, a proteasome inhibitor, an immunomodulatory agent, an anti-CD38 monoclonal antibody, and to the last line of therapy.
In STORM Part 2, a total of 122 patients received XPOVIO 80 mg orally in combination with dexamethasone 20 mg orally on Days 1 and 3 of every week. Treatment continued until disease progression or unacceptable toxicity. Eighty-three patients had RRMM that was refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab. Baseline patient demographics and disease characteristics of these 83 patients are summarized in Table 9 and Table 10, respectively.
Efficacy was based on overall response rate (ORR), as assessed by an Independent Review Committee (IRC) based on the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma. The approval of XPOVIO was based upon the efficacy and safety in a prespecified subgroup analysis of the 83 patients whose disease was refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab, as the benefit-risk ratio appeared to be greater in this more heavily pretreated population than in the overall trial population. Overall response rate results are presented in Table 11. The median time to first response was 4 weeks (range: 1 to 10 weeks). The median duration of response was 3.8 months (95% CI: 2.3, not estimable).
|Median age, years (range)||65 (40, 86)|
|Age category, n (%)|
|<65 years||40 (48)|
|65 – 74 years||31 (37)|
|≥75 years||12 (15)|
|Sex, n (%)|
|Race, n (%)|
|Black or African American||13 (16)|
|Native Hawaiian or other Pacific Islander||1 (1)|
a. Includes any of del(17p)/p53, t(14; 16), t(4; 14), 1q21.
|Median years from diagnosis to start of study treatment (range)||7 (1, 23)|
|Prior treatment regimens, median (range)||8 (4, 18)|
|Documented refractory status, n (%)|
|Documented refractory status to specific combinations, n (%)|
|Bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab||83 (100)|
|Daratumumab in any combination||57 (69)|
|Daratumumab as single agent (+/- dexamethasone)||26 (31)|
|Previous stem cell transplant, n (%)||67 (81)|
|Revised International Staging System at Baseline, n (%)|
|High-risk cytogeneticsa , n (%)||47 (57)|
a. Includes sCR + CR + VGPR + PR.
|Overall Response Rate (ORR) a , n (%)||21 (25.3)|
|95% CI||16.4, 36|
|Stringent Complete Response (sCR)||1 (1)|
|Complete Response (CR)||0|
|Very Good Partial Response (VGPR)||4 (5)|
|Partial Response (PR)||16 (19)|
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