Table 3.

Pharmacokinetics and bioavailability of oral rigosertib

Oral rigosertib plasma PK parameters
70 mg140 mg280 mg560 mg700 mg
ParameterDay 1 (n = 3; mean ± SD)Day 21 (n = 3; mean ± SD)Day 1 (n = 4; mean ± SD)Day 21 (n = 4; mean ± SD)Day 1 (n = 5; mean ± SD)Day 21 (n = 3; mean ± SD)Day 1 (n = 32; mean ± SD)Day 21 (n = 24; mean ± SD)Day 1 (n = 7; mean ± SD)Day 21 (n = 2; mean ± SD)
Cmax (μg/mL)0.40 ± 0.29NA0.20 ± 0.070.43 ± 0.261.84 ± 1.310.73 ± 0.444.04 ± 2.972.54 ± 2.355.93 ± 4.742.34 ± 1.28
P = 0.0463a
AUC0-∞ (μg*h/mL)1.52 ± 1.36NA3.49 ± 5.254.59 ± 4.854.93 ± 4.062.61 ± 1.239.32 ± 6.926.99 ± 5.8819.58 ± 22.954.96 ± 1.71
P = 0.1898a
Tmax (h)1.17 ± 0.29NA1.13 ± 0.250.88 ± 0.251.00 ± 0.350.83 ± 0.581.02 ± 0.321.08 ± 0.411.14 ± 0.481.25 ± 0.35
P = 0.5409a
Vss/F (L)439.4 ± 512.8NA1101.8 ± 424.4787.9 ± 415.4498.5 ± 469.31061.4 ± 603.4314.9 ± 285.2573.8 ± 498.5241.7 ± 211.8472.8 ± 137.5
P = 0.0173a
CL/F (L/h)71.54 ± 42.87NA171.29 ± 155.7455.64 ± 36.62122.84 ± 123.67127.45 ± 66.1393.28 ± 58.24116.33 ± 56.3264.62 ± 34.70149.9 ± 51.79
P = 0.1430a
T1/2 (h)3.34 ± 2.40NA21.56 ± 36.3925.69 ± 38.292.81 ± 0.775.29 ± 1.092.42 ± 1.104.03 ± 2.923.09 ± 2.181.99 ± 0.47
P = 0.0059a

NOTE: Individual patients underwent PK testing after oral dosing on days 1 and 21 of cycle 1. For patients treated at the RP2D of rigosertib (560 mg twice daily), Cmax was significantly lower at steady-state on day 21 than on day 1.

Abbreviations: AUC0-∞, area under the curve determined from time zero extrapolated to infinity; Cmax, maximal concentration; CL/F, clearance Tmax (h), time of peak concentration; T1/2 (h), terminal elimination phase half-life; Vss/F (L), apparent volume of distribution at steady state.

  • aUnpaired t test at 95% confidence interval.