BEXXAR® Clinical
Studies
-
The efficacy of the BEXXAR therapeutic
regimen was evaluated in 2 key studies:
-
A multi-center, single-arm study of 40
patients whose disease had not responded to or had progressed after at least
4 doses of Rituximab therapy
-
A multi-center, single-arm study of 60
chemotherapy refractory patients
Determination of the effectiveness of
the BEXXAR therapeutic regimen is based on overall response rates in patients
whose disease is refractory to chemotherapy and Rituximab. The effects of the
BEXXAR therapeutic regimen on survival are not known
Study Design:
Rituximab Relapsed/Refractory Patients
-
Single-arm, open-label, multi-center
study
-
40 patients whose disease had not
responded to or had progressed after at least 4 doses of Rituximab therapy
-
MIRROR* Panel assessment of response
*
MIRROR Panel: The Masked Independent Randomized
Radiology and Oncology Review panel consists of
two independent
review teams of one oncologist and one radiologist.
Patient
Characteristics N=40
Rituximab
Relapsed/Refractory Study
| Median
Age in Years |
57 |
| Median
# of Prior Chemotherapy Regimens (range) |
4
(1-11) |
Histology
- Low Grade
- Transformed Low Grade
- Intermediate Grade
|
63%
30%
8%
|
| Bone
Marrow Involvement |
30% |
| Bulky
Disease (>5
cm) |
50% |
| Elevated
LDH |
31% |
| Rituximab-refractory
(no response or response < 6 months to last Rituximab |
35
(88%) |
BEXXAR® PI.
Data
on File: GlaxoSmithKline
|
Response Rate and Duration
of Response in All Patients (N=40)
Rituximab Relapsed/Refractory Study
| |
Response Rate %
(95% Cl*) |
Median Duration of
Response
(95% Cl*)
Range (months) |
| Overall Response |
68%
(51%,81%) |
16
Months
(10, NR***months)
1+ to 38+ |
| Complete Response** |
33%
(19%,49%) |
Not
Reached
(15, NR***months)
4 to 38+ |
*
CI = Confidence interval.
** Complete
response rate = Pathologic and clinical complete responses.
***NR
= not reached. Median duration of follow up = 26 months. BEXXAR® PI.
|
Response Rate and Duration
of Response in Rituximab-Refractory Patients (N=35)
Rituximab Relapsed/Refractory Study
| |
Response Rate %
(95% Cl*) |
Median Duration of
Response
|
| Overall Response |
63%
(45%,79%) |
25
Months
(4 to 38+ months) |
| Complete Response** |
29%
(15%,46%) |
Not
Reached
(4 to 38+ months) |
*
CI = Confidence interval.
** Complete
response rate = Pathologic and clinical complete responses.
***NR
= not reached. Median duration of follow up = 26 months. BEXXAR® PI.
|
Study Design:
Chemotherapy Refractory Patients
- Single-arm, open-label, multi-center
study
- 60 patients with CD20 positive low-grade
or transformed low-grade non-Hodgkin's lymphoma whose disease failed to
respond to or progressed within 6 months after their last qualifying
chemotherapy (LQC) regimen
- MIRROR* Panel assessed clinical outcomes
of BEXXAR®, based on:
- Overall response
- Complete response
- Duration of response
*
MIRROR Panel: The Masked Independent Randomized
Radiology and Oncology Review panel consists of two
independent
review teams of one oncologist and one radiologist.
Patient Characteristics
(N=60)
Chemotherapy Refractory Study
| Median
Age in Years |
60 |
| Median
# of Prior Chemotherapy Regimens (range) |
4
(2-13) |
Histology
- Low Grade
- Transformed Low Grade
- Intermediate Grade
|
60%
38%
2%
|
| Bone
Marrow Involvement |
56% |
| Bulky
Disease (>5
cm) |
38% |
| Elevated
LDH |
44% |
| Response
to last chemotherapy regimen |
ORR
(12%)
CR (2%) |
BEXXAR® PI.
Data
on File: GlaxoSmithKline
|
Response Rate and Duration
of Response in Chemotherapy-Refractory Patients (N=60)
Chemotherapy Refractory Study
| |
Response Rate %
(95% Cl*) |
Median Duration of
Response
(95% Cl*)
Range (months) |
| Overall Response |
47%
(34%,60%) |
12
Months
(7, 47 months)
2-47 |
| Complete Response** |
20%
(11%,32%) |
47
Months
(15, NR***months)
9 to 47 |
*
CI = Confidence interval.
** Complete
response rate = Pathologic and clinical complete responses.
***NR
= not reached. Median duration of follow up = 26 months. BEXXAR® PI.
|
Additional Clinical Studies
Demonstrating Durable Objective Responses
-
The
results of the 2 key studies were supported by demonstration of durable
abjective responses in three single-arm studies.
-
In
these studies, 130 patients with Rituximab-naive follicular non-Hodgkin's
lymphoma with or without transformation were evaluated for efficacy.
|
Study Description |
| Phase I/II study of
chemotherapy-relapsed or refractory NHL |
| Phase II study of
chemotherapy-relapsed or refractory low-grade NHL |
| Randomized Study of Bexxar
versus Tositumomab |
Additional Clinical Studies
Demonstrating Durable Response in Low-Grade, or Follicular NHL
| |
Median Months of Follow- Up
(range) |
Response Rate %
(95% Cl*) |
Median Duration of
Response
(months,range) |
| Phase II chemotherapy
relapsed or refractory n=47 |
34
(0,97) |
49%
(34%,64%) |
13
(1+, 60+) |
Bexxar®
vs Tositumomab**
n=61 |
45
(2,72) |
59%
(46%,71%) |
13
(2, 57) |
| Phase I/II chemotherapy
relapsed or refractory*** n=22 |
46
(2,128) |
64%
(41%,83%) |
16
(3, 94) |
|
*
CI =
Confidence interval.
** Includes
patients randomized to BEXXAR and patients crossing over to BEXXAR
***Includes
patients with low-grade NHL with or without transformation prescribed a
65 or 75 cGy total body dose
Due to small sample sizes in the supportive studies, as in the
chemotherapy refractory and rituximab refractory studies, the 95%
confidence intervals for the median duration on response are wide.
BEXXAR® PI.
|
Conclusions
