Table 2.

Selected mean (SD) pharmacokinetic parameters for antibody-conjugated MMAE, total antibody, and unconjugated MMAE after cycle 1 of pinatuzumab vedotin in pharmacokinetic-evaluablea NHL patients

Conjugate (evaluated as acMMAE)
Dose (mg/kg)No. of patientsaCmax (ng/mL)AUCinf (ng/mL) * dayt1/2 (day)Vss (mL/kg)CL (mL/kg per day)
0.1341.4 (14.2)65.6 (16.6)3.59 (1.96)83.1 (29.7)28.6 (8.44)
0.25462 (16.1)117 (46.9)4.29 (4.12)133 (72.2)42.8 (19.2)
0.56164 (41.2)335 (155)6.36 (5.45)123 (80.4)30.6 (12.1)
13414 (139)895 (274)4.42 (1.12)78 (22.1)21.0 (5.75)
1.87588 (124)1,710 (482)6.69 (0.99)117 (26.5)19.5 (4.84)
2.46834 (206)2,440 (964)8.18 (2.08)111 (31.6)25.7 (25.8)
3.231,060 (216)3,400 (1,070)8.44 (3.62)120 (46)17.9 (6.48)
2.4 (DLBCL expansion)22884 (225)2,420 (661)6.36 (2.75)102 (31.6)19.5 (9.48)
2.4 (iNHL expansion)11890 (302)2,130 (1,010)4.72 (2.14)99.5 (38.9)24.3 (11.2)
1.8 (combination with rituximab)5548 (160)1,360 (552)6.68 (2.59)156 (93.6)27.7 (12.4)
2.4 (combination with rituximab)11886 (236)2,890 (1,110)5.17 (1.9)79.7 (12.8)19.2 (17.2)
Total antibody
Dose (mg/kg)No. of patientsaCmax (ng/mL)AUCinf (ng/mL) * dayt1/2 (day)Vss (mL/kg)CL (mL/kg per day)
0.131,920 (496)5,790 (1,660)4.48 (2.21)96.4 (31.2)18.5 (5.36)
0.2543,840 (851)12,600 (7,120)4.99 (4.24)112 (33.9)26.1 (16.6)
0.566,920 (1,920)30,800 (20,000)8.37 (7.44)152 (69.8)24.1 (16.3)
1317,800 (8,790)63,000 (13,500)5.91 (1.6)122 (21.6)16.6 (3.64)
1.8728,000 (5,660)180,000 (51,000)11.9 (3.93)153 (34.7)10.6 (2.8)
2.4639,100 (11,800)247,000 (109,000)11.6 (5.59)145 (36)20.8 (30.7)
3.2350,900 (19,600)316,000 (109,000)11.1 (8.2)163 (128)10.8 (3.12)
2.4 (DLBCL expansion)2141,600 (11,300)276,000 (103,000)12.2 (6.49)131 (39.2)11.4 (9.85)
2.4 (iNHL expansion)1145,400 (17,000)219,000 (106,000)7.39 (4.04)113 (43.5)14.2 (8.35)
1.8 (combination with rituximab)526,000 (7,360)154,000 (78,500)12.3 (6.85)191 (131)14.1 (5.62)
2.4 (combination with rituximab)1141,300 (14,500)308,000 (95,800)9.24 (3.11)94.2 (18.5)7.57 (1.79)
Unconjugated MMAEb
Dose (mg/kg)No. of patientsaCmax (ng/mL)AUCinf (ng/mL) * dayt1/2 (day)tmax (day)
0.130.32 (0.2)4.152.671.72 (1.17)
0.2540.37 (0.16)2.88 (1.57)3.75 (0.63)1.53 (0.95)
0.560.86 (0.95)6.74 (8.29)3.11 (0.41)2.14 (1.28)
131.82 (0.84)14.6 (6.93)2.94 (0.36)3.29 (0.49)
1.872.92 (1.49)30.1 (14.7)4.08 (0.93)3.55 (0.58)
2.465.55 (3.26)43 (16.7)3.46 (0.63)3.54 (1.97)
3.239.83 (5.01)104 (50.9)4.07 (1.43)4.28 (3.05)
2.4 (DLBCL expansion)227.15 (5.95)54.1 (38.2)3.85 (1)3.99 (1.41)
2.4 (iNHL expansion)115.62 (2.39)50.9 (29.9)3.39 (0.75)2.87 (1.33)
1.8 (combination with rituximab)54.10 (2.2)37.0 (29.0)4.52 (1.36)3.17 (1.73)
2.4 (combination with rituximab)115.36 (4.24)41.5 (30.9)3.91 (0.33)4.1 (1.52)
  • NOTE: Data are mean (SD). Table shows data for pharmacokinetic-evaluable patients with NHL (i.e., those with at least one pharmacokinetic parameter estimated). Clearance refers to dose divided by area under the concentration–time curve.

  • Abbreviations: AUCinf, area under the concentration–time curve from time 0 extrapolated to infinity; Cmax, maximum observed concentration; CL, clearance; t1/2, terminal half-life; tmax, time to reach maximum concentration; Vss, volume of distribution at steady state.

  • aNumber of patients with at least one pharmacokinetic parameter estimated.

  • bClearance and Vss values are not estimated because the fraction of conversion of pinatuzumab vedotin to the unconjugated MMAE metabolite is unknown.