Table 2.
Assessment of CHP as a perpetrator of a PK drug–drug interaction with 1.8 mg/kg of pola as a victim based on cycle 1 non-compartmental analysis results
| Analyte | Parameter | N | GO29044 (pola + R-CHP) DLBCL | N | GO27834 (pola + R) FL | GMR (90% CI) |
|---|---|---|---|---|---|---|
| acMMAE | Cmax (ng/mL) | 36 | 503 (36.4) | 17 | 780 (14.4) | 0.646 (0.576–0.724) |
| AUCinf (ng day/mL) | 28 | 1800 (28.5) | 15 | 2530 (25.9) | 0.711 (0.616–0.820) | |
| Unconjugated MMAE | Cmax (ng/mL) | 35 | 2.43 (37.9) | 20 | 1.75 (54.3) | 1.39 (1.11–1.73) |
| AUClast (ng day/mL) | 27 | 22.6 (40.4) | 20 | 15.8 (50.1) | 1.43 (1.15–1.78) |
| Analyte | Parameter | N | GO29044 (pola + G-CHP) DLBCL | N | GO27834 (pola + G) DLBCL | GMR (90% CI) |
|---|---|---|---|---|---|---|
| acMMAE | Cmax (ng/mL) | 17 | 513 (26.6) | 33 | 694 (22.7) | 0.739 (0.651–0.839) |
| AUCinf (ng day/mL) | 11 | 1890 (23.7) | 26 | 2350 (28.4) | 0.805 (0.691–0.938) | |
| Unconjugated MMAE | Cmax (ng/mL) | 14 | 2.44 (60.0) | 40 | 2.68 (81.1) | 0.911 (0.664–1.25) |
| AUClast (ng day/mL) | 10 | 20.4 (62.8) | 40 | 22.5 (70.7) | 0.907 (0.629–1.31) |
All values are geometric mean (% geo CV), except for GMR
acMMAE antibody-conjugated MMAE, AUCinf area under the concentration–time curve from 0 to infinity, AUClast area under the concentration–time curve from 0 until the last measurable time point, CHP cyclophosphamide, doxorubicin, and prednisone, CI confidence interval, Cmax maximum concentration, CV coefficient of variation, DLBCL diffuse large B-cell lymphoma, FL follicular lymphoma, G obinutuzumab, G-CHP obinutuzumab, cyclophosphamide, doxorubicin, and prednisone, GMR geometric mean ratio, MMAE monomethyl auristatin E, PK pharmacokinetic, pola polatuzumab vedotin, R rituximab, R-CHP rituximab, cyclophosphamide, doxorubicin, and prednisone