Table 1.
Summary statistics for dostarlimab pharmacokinetic parameters, cycle 1 for parts 1 and 2A
| Part 1: Geometric mean (GCV%) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| AUC(0-∞) (µg·h/mL) |
AUC(0-τ) (µg·h/mL) |
Cmax (µg/mL) |
tmaxa (h) |
Ctroughb (µg/mL) |
t1/2 (d) |
CL (L/d) |
Vz (L) |
Vss (L) |
||
|
1 mg/kg, DLT-eval (n = 3) |
4440–9570c | 3417 (31.7) | 21.78 (25.6) | 2.92 (1.52–2.95) | 6.382 (35.9) | 8.2–14.2c | 0.336–0.367c | 3.97–7.50c | 4.12–7.29c | |
|
1 mg/kg, PK/PDy (n = 3) |
5872 (93.3) | 4219 (63.8) | 20.43 (17.7) | 1.50 (0.55–1.50) | 2.622 (148.4) | 14.5 (67.1) | 0.326 (64.8) | 6.84 (7.6) | 6.73 (17.8) | |
|
3 mg/kg (n = 3) |
26,630 (9.4) | 10,790 (9.7) | 66.17 (9.6) | 1.52 (1.50–2.95) | 23.70 (8.9) | 19.1 (23.8) | 0.189 (33.5) | 5.20 (33.5) | 5.11 (32.1) | |
|
10 mg/kg, DLT-eval (n = 6) |
59,830 (26.7) | 36,480 (24.4) | 228.4 (22.2) | 1.52 (1.50–3.07) | 60.63 (34.7) | 10.2 (35.5) | 0.302 (22.3) | 4.43 (18.3) | 4.33 (19.8) | |
|
10 mg/kg, PK/PDy (n = 6) |
101,900 (35.8)d | 63,670 (28.2)d | 251.1 (19.2) | 1.50 (1.43–3.12) | 53.15 (35.0)d | 20.5 (18.2)d | 0.160 (13.6)d | 4.73 (14.2)d | 4.57 (14.0)d | |
| Part 2A: Geometric mean (GCV%) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| AUC(0-∞) (µg·h/mL) |
AUC(0-τ)e (µg·h/mL) |
Cmax (µg/mL) |
tmaxa (h) |
Ctroughf (µg/mL) |
t1/2 (d) |
CL (L/d) |
Vz (L) |
Vss (L) |
|
|
500 mg Q3W (n = 6) |
55,510 (24.2) | 35,730 (20.2) | 171.1 (20.0) | 0.96 (0.50–3.02) | 39.17 (26.7) | 14.5 (12.3) | 0.216 (24.2) | 4.51 (20.5) | 4.38 (18.0) |
|
1000 mg Q6W (n = 7) |
113,500 (34.4) | 95,820 (29.3)d | 309.4 (30.8) | 1.52 (0.52–3.00) | 40.20 (51.1)c | 19.6 (21.9) | 0.212 (34.4) | 5.97 (31.9) | 5.77 (29.8) |
AUC area under the serum dostarlimab concentration–time curve, DLT-eval dose-limiting toxicity-evaluable, GCV% geometric coefficient of variation, ND not determined, PK/PDy pharmacokinetics/pharmacodynamics, Vz volume of distribution during terminal elimination
Note that AUC(0-τ) is calculated based on the 28 days for PK/PDy patients and 14 days for all other patients
aMedian (range)
bCtrough at nominal time of 336 h for DLT-evaluable patients and 504 h for PK/PDy patients
cn = 2; only minimum and maximum presented
dn = 5
eAUC(0-τ) is identical to AUC(0-last), and hence only one parameter is presented
fCtrough at nominal of 504 h for patients with Q3W dosing and 1008 h for patients with Q6W dosing