Table 1.
Clinical Samples used for Pharmacodynamic Analysis
| Blood and PBMC pharmacodynamic samples from MM patientsa | ||||
| Trialb | Phase | N | 2‐ to 10‐min infusion dose (initial/escalation mg/m2) | 30‐min infusion dose (initial/escalation mg/m2) |
|
PX‐171‐005 (NCT00721734) |
II | 31 | 15/20 (N = 31) | – |
|
PX‐171‐006 (NCT00603447) |
Ib/II | 16 |
15 only (n = 8) 20/27 (n = 8) |
– |
|
PX‐171‐007 (NCT00531284) |
I/II | 24 |
20/36 (n = 3) 20/45 (n = 3) 20/56 (n = 19) |
|
| Bone marrow pharmacodynamic samples from MM patientsc | ||||
| Trialb | Phase | N | 2‐ to 10‐min infusion dose (mg/m2) | 30‐min infusion dose (mg/m2) |
|
PX‐171‐003‐A0 and ‐A1 (NCT00511238) |
II | 7 |
20 only (N = 7; predose, n = 3; C1D2, n = 4) |
— |
|
PX‐171‐004 (NCT00530816) |
II | 11 |
20 only (N = 11; predose, n = 6; C1D2, n = 5) |
— |
|
PX‐171‐005 (NCT00721734) |
II | 15 |
Dose N/A (MM, N = 15; predose, n = 15; C1D2, n = 0) |
— |
| Blood and PBMC pharmacodynamic samples from ST patientsa | ||||
|
PX‐171‐007 (NCT00531284) |
I/II | 36 |
20 only (n = 3) 20/27 (n = 3) 20/36 (n = 18) |
20/45 (n = 2) 36 only (n = 6) 45 only (n = 6) |
C, cycle; D, day; MM, multiple myeloma; N/A, not applicable; PBMC, peripheral blood mononuclear cell; ST, solid tumour.
a
cycle 1, multiple days, and cycle 2, day 1 only.
b
Blood and/or bone marrow aspirates were collected from patients in five clinical trials prior to and after carfilzomib treatment and at the doses listed. Samples were analysed for proteasome activity and subunit occupancy as described in Fig 1.
c
Predose and C1, D2 only.