Table 4.
Assessment of 1.8 mg/kg of pola as a perpetrator of a PK drug–drug interaction with cyclophosphamide, doxorubicin, rituximab, and obinutuzumab as a victim based on descriptive statistics of exposure comparisons
| DDI victim | Tx | Parameter | N | GO29044 (C1D1) Before pola dosing |
N | GO29044 (C3D1) After pola dosing |
GMR (90% CI) |
|---|---|---|---|---|---|---|---|
| Cyclophosphamide (µg/mL) | R-CHP | C23h | 25 | 2.64 (56.2) | 19 | 2.67 (74.8) | 1.01 (0.737–1.38) |
| G-CHP | C23h | 14 | 3.00 (52.4) | 14 | 2.83 (50.1) | 0.943 (0.691–1.29) | |
| Doxorubicin (ng/mL) | R-CHP | C24h | 25 | 8.79 (29.1) | 20 | 8.43 (25.8) | 0.959 (0.838–1.10) |
| G-CHP | C24h | 12 | 9.44 (60.6) | 14 | 8.94 (21.3) | 0.947 (0.701–1.28) |
| DDI victim | Tx | Parameter | n | BO22334 R-CHOP |
n | GO29044 Pola + R-CHP |
GMR (90% CI) |
|---|---|---|---|---|---|---|---|
| Rituximab (µg/mL) | R-CHP | C4 pre-dose | 189 | 45.0 (111) | 28 | 66.3 (36.2) | 1.47 (1.26–1.72) |
| DDI victim | Tx | Parameter | n | BO21003 G |
n | GO29044 Pola + G-CHP |
GMR (90% CI) |
|---|---|---|---|---|---|---|---|
| Obinutuzumab (µg/mL) | G-CHP | C2 pre-dose | 74 | 378 (60.5) | 15 | 266 (71.0) | 0.703 (0.517–0.955) |
All values are geometric mean (% geo CV), except for GMR. GO29044 = 1L DLBCL; BO21003 = R/R indolent B-cell NHL; and BO22334 = 1L FL
1L first line, C cycle, C23h concentration 23 h after dosing with DDI victim, C24h concentration 24 h after dosing with DDI victim, CI confidence interval, CV coefficient of variation, D day, DDI drug–drug interaction, DLBCL diffuse large B-cell lymphoma, FL follicular lymphoma, G obinutuzumab, G-CHP obinutuzumab, cyclophosphamide, doxorubicin, and prednisone, GMR geometric mean ratio, NHL non-Hodgkin lymphoma, PK pharmacokinetic, pola polatuzumab vedotin, R-CHOP rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, R-CHP rituximab, cyclophosphamide, doxorubicin, and prednisone, R/R relapsed/refractory, tx treatment