● Biodistribution Images
| Normal Biodistribution |
Total body residence time-
50 - 150 hours
First Image
(shortly after dosimetric dose)
Most activity in the blood pool
(heart and major blood vessels)
Uptake in liver and spleen is < in heart |
Total body residence time
50 - 150 hours
Second Image
(2-4 days after dosimetric dose)
Decreased activity in blood pool
Decreased accumulation of
activity in liver and spleen |
Total body residence time
50 - 150 hours
Third Image
(6-7 days after dosimetric dose)
Significantly decreased activity in blood pool, liver and spleen
Altered biodistributionbest seen |
|
Expected Biodistribution: Porta Catheter |
|
Expected Biodistribution: Stomach and Thyroid Uptake |
|
| Expected Biodistribution: Mid Abdominal Retroperitoneal Tumor |
|
| Expected Biodistribution: Left Supraclavicular and Skull Tumor |
|
| Expected Biodistribution: Cutaneous T-Cell Lymphoma |
|
| Altered Biodistribution: Splenomegaly with Increased Uptake |
|
● Clinical Studies
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
Overall response
Complete response
Median 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=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%
28%
2%
|
| Bone Marrow Involvement |
56% |
| Bulky Disease (> or = to 5 cm) |
38% |
| Elevated LDH |
44% |
| Response to last chemotherapy regimen |
|
| 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 to 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 |
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
● In 2 key studies, BEXXAR® has demonstrated efficacy in patients with CD20 positive relapsed or refractory follicular, low grade or transformed non-Hodgkin’s lymphoma:
Overall response rates: 47%-68%
Complete response rate: 20%-33%
Median duration of response: 12-16 months
Median duration of CR: 47 months-Not Reached
Range: (4, 47 months)
Median duration of follow up = 26-30 months
