Table 3.
PK Parameters of Ser-T and AM-1 S238C (Total Ab) on Cycle 1 or Cycle 3
| Dosing | Dose µg/mL |
N |
C
max
ng/mL |
T
max
a
h |
AUCt h*µg/mL |
AUCinf h*µg/mL |
t
1/2
b
day |
CLc mL/h/kg |
V
d
d
mL/kg |
DN-Cmax ng/mL per µg/kg |
DN-AUCt h*ng/mL per µg/kg |
DN-AUCinf h*ng/mL per µg/kg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q4W | Ser-T first infusion (cycle 1) intensive PK | |||||||||||
| 5 | 1 | 68.8 | 2 | 2.85 | 3.33 | 1.5 | 1.50 | 75.5 | 13.8 | 570 | 666 | |
| 10 | 2 | 174, 177 | 2, 4 | 6.57, 7.33 | 7.92, 9.90 | 1.7, 2.2 | 1.01, 1.26 | 73.4, 75.1 | 17.4, 17.7 | 657, 733 | 792, 990 | |
| 20 | 3 | 329 (330, 8.0) |
2 (2, 4) |
15.9 (16.3, 28) |
16.9 (17.2, 26) |
2.2 ± 0.64 | 1.19 (1.21, 23) |
92.5 (93.0, 12) |
16.5 (16.5, 8.0) |
795 (814, 28) |
843 (860, 26) |
|
| 30 | 5 | 470 (483, 26) |
2 (2, 2) |
23.0 (26.9, 74) |
24.6 (28.4, 70) |
2.0 ± 0.64 | 1.22 (1.35, 41) |
88.6 (89.7, 16) |
15.7 (16.1, 26) |
766 (896, 74) |
819 (948, 70) |
|
| 40 | 5 | 647 (684, 40) |
2 (2, 2) |
34.7 (36.4, 34) |
36.4 (37.9, 32) |
2.6 ± 0.91 | 1.10 (1.15, 32) |
105 (108, 27) |
16.2 (17.1, 40) |
868 (910, 34) |
909 (948, 32) |
|
| 50 | 26 | 882 (924, 33) |
2 (2, 4) |
45.3 (47.9, 33) |
47.1 (49.7, 32) |
2.7 ± 1.4 | 1.06 (1.13, 39) |
107 (115, 41) |
17.6 (18.5, 33) |
905 (959, 33) |
943 (995, 32) |
|
| Overall | 42 | – | 2 (2, 4)e |
– | – | 2.4 ± 1.1 | 1.10 (1.17, 35) |
101 (107, 38) |
17.0 (17.7, 31) |
854 (913, 38) |
906 (961, 36) |
|
| Q4W | AM-1 S238C (total Ab) first infusion (cycle 1) intensive PK | |||||||||||
| 5 | 1 | 69.1 | 2 | 4.27 | 4.81 | 2.1 | 1.04 | 75.2 | 13.8 | 855 | 962 | |
| 10 | 2 | 184, 194 | 2, 4 | 16.2, 9.23 | 17.6, 10.1 | 4.0, 2.1 | 0.570, 0.995 | 79.5, 71.5 | 18.4, 19.4 | 1620, 923 | 1760, 1010 | |
| 20 | 3 | 341 (343, 11) |
2 (2, 4) |
20.3 (20.7, 25) |
21.6 (22.0, 23) |
3.0 ± 1.1 | 0.925 (0.940, 21) |
97.8 (99.2, 21) |
17.1 (17.1, 11) |
1010 (1030, 25) |
1080 (1100, 23) |
|
| 30 | 5 | 449 (465, 31) |
2 (2, 4) |
26.0 (31.8, 84) |
27.9 (33.8, 81) |
2.4 ± 0.91 | 1.07 (1.21, 44) |
94.7 (97.7, 26) |
15.0 (15.5, 31) |
868 (1060, 84) |
932 (1130, 81) |
|
| 40 | 5 | 685 (715, 33) |
2 (2, 2) |
39.2 (40.9, 33) |
41.5 (43.2, 32) |
3.3 ± 1.2 | 0.965 (1.00, 32) |
115 (120, 32) |
17.1 (17.9, 33) |
980 (1020, 33) |
1040 (1080, 32) |
|
| 50 | 26 | 917 (978, 42) |
2 (2, 4) |
59.9 (70.0, 68) |
71.5 (106, 131) |
3.3 ± 2.5 | 0.699 (0.853, 54) |
97.9 (107, 43) |
18.3 (19.6, 42) |
1200 (1400, 68) |
1430 (2120, 131) |
|
| Overall | 42 | – | 2 (2, 4)e |
– | – | 3.1 ± 1.8 | 0.790 (0.922, 47) |
97.5 (104, 38) |
17.6 (18.5, 38) |
1100 (1270, 65) |
1270 (1740, 129) |
Ab, antibody; AUC, area under the plasma concentration-time curve; AUCinf, AUC from time 0 to infinity; AUCt, AUC from time 0 to time of last measurable concentration; Cmax, maximum observed plasma concentration; CL, clearance; DN, dose-normalized to cohort dose; PK, pharmacokinetic; Q4W, once every 4 weeks; Ser-T, serclutamab talirine; Tmax, time to Cmax; t1/2, terminal phase elimination half-life; SD, standard deviation;.Vd, volume of distribution.
N >3 presented as geometric mean (mean, %CV); N = 2 presented individual values; N = 1 presented as individual value.
aMedian (min, max).
bHarmonic mean ± pseudo SD.
cCL for first infusion is calculated as dose/AUCinf.
d Vd is calculated on the basis of respective clearance after the first or third infusion.
e N = 38, excluded patients (n = 4) due to Tmax >24 h (first sampling).