Table 5.
Literature overview of previous PK model parameters for PD-1 inhibitors
| Data source | N | Obs.(obs./pt.) | Dose range | PK model | CL (L/day) | Vc (L) | Vp (L) | Q (L/day) | Variance of CL (CV%) | Covariates tested | Covariates in model | Reference |
| Pembrolizumab: | ||||||||||||
| Trial* | 1223 | 10.0 | 1–10 mg/kg Q3W | 2-comp, LE | 0.22 | 3.48 | 4.06 | 0.795 | 38 | Age, gender, ethnicity, renal function, liver tests, albumin, glucocorticoid use, prior treatment, tumor type, PS, TB | Albumin (neg on CL), PS (neg on CL), renal function (pos on CL), prior ipilimumab (pos on CL), gender (female: neg on CL), TB (pos on CL) | Ahamadi et al21 |
| Trial† | Not given | – | 0.02–10 mg/kg Q3W |
2-comp, LE+NLE | 0.168 | 2.88 | 2.85 | 0.384 | 28.8 | – | – | Elassais-Schaap et al23 |
| Trial† | 2841 | 6.1 | 1–10 mg/kg Q3W | 2-comp, LE, TV | 0.249 | 3.47 | 2.96 | 0.889 | 30.7 | Age, gender, ethnicity, body weight, renal function, liver tests, glucocorticoid use, PS, geographics, smoking, PD-L1, lymphocyte count (TV), LDH (TV), albumin (TV), TB (TV) | Albumin (neg on CL), bilirubin (neg on CL), renal function (pos on CL), PS (pos on CL), gender (female: neg on CL), TB (pos on CL) | Li et al24 |
| Nivolumab: | ||||||||||||
| Real-world | 221 | 7.8 | 3 mg/kg Q2W | 2-comp, LE | 0.211 | 3.46 | 3.46 | 0.48 | 30.7 | Age, gender, ethnicity, body weight, BSA, renal function, total serum protein, albumin, LDH, tumor type, PS, TB, leukocyte count | Gender (female: neg on CL), BSA (pos on CL), albumin (neg on CL) | Hurkmans et al19 |
| Trial‡ | 1895 | 0.1–20 mg/kg Q2W | 2-comp, LE | 0.23 | 3.63 | 2.78 | 0.770 | 35 | Age, gender, ethnicity, body weight, renal function, liver tests, PS, TB, LDH, tumor type, PD-L1 | Body weight (pos on CL), renal function (pos on CL), performance (pos on CL), ethnicity (asian: neg on CL), gender (female: neg on CL) | Bajaj et al22 | |
Population PK parameters of previous models for PD-1 inhibitors (i.e. pembrolizumab and nivolumab).
*KEYNOTE-001,–002, and −006.
†KEYNOTE-010.
‡Pooled data from eleven phase I-III.
BSA, body surface area; CL, systemic clearance; LDH, lactate dehydrogenase; LE, linear elimination; NLE, non-linear elimination; obs, observations; PD-L1, programmed cell death protein 1; PS, performance status; Q3W or Q2W, 3 or 2 weekly; TB, tumor burden; TV, time variance; Vc or Vp, central or peripheral volume of distribution.