Table 3.

Pharmacokinetics and bioavailability of oral rigosertib

Oral rigosertib plasma PK parameters
	70 mg		140 mg		280 mg		560 mg		700 mg
Parameter	Day 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)
C_max (μg/mL)	0.40 ± 0.29	NA	0.20 ± 0.07	0.43 ± 0.26	1.84 ± 1.31	0.73 ± 0.44	4.04 ± 2.97	2.54 ± 2.35	5.93 ± 4.74	2.34 ± 1.28
							P = 0.0463^a
AUC_0-∞ (μg*h/mL)	1.52 ± 1.36	NA	3.49 ± 5.25	4.59 ± 4.85	4.93 ± 4.06	2.61 ± 1.23	9.32 ± 6.92	6.99 ± 5.88	19.58 ± 22.95	4.96 ± 1.71
							P = 0.1898^a
T_max (h)	1.17 ± 0.29	NA	1.13 ± 0.25	0.88 ± 0.25	1.00 ± 0.35	0.83 ± 0.58	1.02 ± 0.32	1.08 ± 0.41	1.14 ± 0.48	1.25 ± 0.35
							P = 0.5409^a
V_ss/F (L)	439.4 ± 512.8	NA	1101.8 ± 424.4	787.9 ± 415.4	498.5 ± 469.3	1061.4 ± 603.4	314.9 ± 285.2	573.8 ± 498.5	241.7 ± 211.8	472.8 ± 137.5
							P = 0.0173^a
CL/F (L/h)	71.54 ± 42.87	NA	171.29 ± 155.74	55.64 ± 36.62	122.84 ± 123.67	127.45 ± 66.13	93.28 ± 58.24	116.33 ± 56.32	64.62 ± 34.70	149.9 ± 51.79
							P = 0.1430^a
T_1/2 (h)	3.34 ± 2.40	NA	21.56 ± 36.39	25.69 ± 38.29	2.81 ± 0.77	5.29 ± 1.09	2.42 ± 1.10	4.03 ± 2.92	3.09 ± 2.18	1.99 ± 0.47
							P = 0.0059^a

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), C_max was significantly lower at steady-state on day 21 than on day 1.

Abbreviations: AUC_0-∞, area under the curve determined from time zero extrapolated to infinity; C_max, maximal concentration; CL/F, clearance T_max (h), time of peak concentration; T_1/2 (h), terminal elimination phase half-life; V_ss/F (L), apparent volume of distribution at steady state.

↵^aUnpaired t test at 95% confidence interval.