Table 3.
Mean pharmacokinetic parameters for treatment groups of dostarlimab after intravenous infusion to monkeys at day 1 and day 22 in 1-month repeat-dose toxicology study
| Dose (mg/kg) | Study day | Sex | Cmax (μg/mL) | Tmax (h) | t1/2 (h) | AUC0–168 (h*μg/mL) |
|---|---|---|---|---|---|---|
| 10 | 1 | Male | 257 ± 77.8 | 0.5 (0.5–4.0) | 260.1 (140.7–597.2) | 17,700 ± 3870 |
| Female | 273 ± 27.2 | 0.5 (0.5–4.0) | 211.9 (133.9–346.6) | 19,800 ± 2620 | ||
| Combined | 265 ± 56.1 | 0.5 (0.5–4.0) | 211.9 (133.9–597.2) | 18,800 ± 3340 | ||
| 22 | Male | 451 ± 33.5 | 0.5 (0.5–0.5) | 249.3 (191.3–424.3) | 54,600 ± 5110 | |
| Female | 488 ± 49.3 | 0.5 (0.5–4.0) | 187.3 (175.3–542.3) | 54,300 ± 8540 | ||
| Combined | 469 ± 44.5 | 0.5 (0.5–4.0) | 217.8 (175.3–542.3) | 54,400 ± 6710 | ||
| 30 | 1 | Male | 691 ± 76.6 | 0.5 (0.5–0.5) | 184.5 (109.4–294.1) | 54,300 ± 5730 |
| Female | 873 ± 77.6 | 4.0 (0.5–8.0) | 137.7 (107.8–224.0) | 68,000 ± 9350 | ||
| Combined | 782 ± 120 | 0.5 (0.5–8.0) | 174.9 (107.8–294.1) | 61,200 ± 10,300 | ||
| 22 | Male | 1260 ± 251 | 4.0 (0.5–8.0) | 443.6 (111.8–810.2) | 147,000 ± 57,700 | |
| Female | 1380 ± 197 | 4.0 (0.5–8.0) | 222.0 (192.9–438.6) | 147,000 ± 22,100 | ||
| Combined | 1320 ± 224 | 4.0 (0.5–8.0) | 318.2 (111.8–810.2) | 147,000 ± 41,700 | ||
| 100 | 1 | Male | 2380 ± 475 | 0.5 (0.5–0.5) | 227.5 (165.5–305.1) | 193,000 ± 14,800 |
| Female | 2850 ± 718 | 0.5 (0.5–8.0) | 144.1 (110.3–191.0) | 201,000 ± 16,800 | ||
| Combined | 2620 ± 630 | 0.5 (0.5–8.0) | 172.3 (110.3–305.1) | 197,000 ± 15,600 | ||
| 22 | Male | 4080 ± 313 | 4.0 (4.0–8.0) | 286.6 (161.2–468.6) | 473,000 ± 69,000 | |
| Female | 4060 ± 1470 | 0.5 (0.5–8.0) | 175.3 (57.1–266.0) | 365,000 ± 191,000 | ||
| Combined | 4070 ± 1010 | 4.0 (0.5–8.0) | 212.8 (57.1–468.6) | 419,000 ± 148,000 |
Data are presented as mean ± standard deviation for Cmax and AUC0–168 values, and median (range) for Tmax and t1/2 values. AUC0–168: area under the concentration–time curve from time 0 to 168 hours; Cmax: maximum concentration; t1/2: half-life; Tmax: time to Cmax.