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MANIFEST (NCT02158858) is a phase II clinical trial of CPI-0610, a small molecule inhibitor of bromodomain and extraterminal (BET) proteins, with and without ruxolitinib, a selective inhibitor of the Janus-associated tyrosine kinases (JAK) 1 and 2, in patients with myelofibrosis (MF). Coverage of the previous report from the American Society of Hematology (ASH) Annual Meeting and Exhibition 2019 can be found here. This report is from a larger data set presented at the European Hematology Association (EHA) annual 2020 virtual meeting and may supersede the data in the published abstracts.
Table 1. Best response data after 24-weeks1,2,
rux, ruxolitinib; SVR35, spleen volume response of 35% reduction from baseline; TD, transfusion dependent; TI, transfusion independent; TSS50, 50% improvement in total symptom score |
||||
Best responses |
Arm 1 CPI-0610 monotherapy (N = 43) |
Arm 2 CPI-0610 + rux (N = 70) |
||
---|---|---|---|---|
TD patients (n = 16) |
TI patients (n = 27) |
TD patients (n = 44) |
TI patients (n = 26) |
|
SVR35 response, % (n/N) |
0.0% (0/10) |
23.8 (5/21) |
20.8 (5/24) |
22.2 (4/18) |
TD to TI conversion, % (n/N) |
21.4% (3/14) |
— |
34.4% (11/32) |
— |
TSS50 response, % (n/N) |
8.3 (1/12) |
47.4 (9/19) |
46.2 (12/26) |
36.8 (7/19) |
≥ 1.5 g/dL mean increase in hemoglobin, % (n/N) |
57.9% (11/19) |
— |
— |
— |
Table 2. Best responses of Arm 3 at 12 and 24 weeks3
JAKi, Janus-associated tyrosine kinase inhibitor; rux, ruxolitinib; SVR35, spleen volume response of 35% reduction from baseline; TD, transfusion dependent; TI, transfusion independent; TSS50, 50% improvement in total symptom score |
||
Best responses |
Arm 3 CPI-0610 + rux JAKi-naïve |
|
---|---|---|
12 weeks |
24 weeks |
|
SVR35 response, % (95% CI) |
72.5 (58.3, 84.1) |
63.3 (43.9, 80.1) |
Median spleen volume reduction, % |
50.8% |
52.9% |
TSS50 response, % (95% CI) |
58.0 (43.2, 71.8) |
58.6 (38.9, 76.5) |
Median TSS improvement, % |
57.0% |
64.0% |
Table 3. Safety analysis of TEAEs per study arm1,2,3
TEAE, treatment-emergent adverse event |
|||
Safety analysis |
Arm 1 (n = 43) |
Arm 2 (n = 70) |
Arm 3 (n = 64) |
---|---|---|---|
Grade 3 TEAE, % |
|
|
|
Thrombocytopenia |
14.0 |
22.9 |
1.6 |
Anemia |
9.3 |
7.1 |
15.6 |
Diarrhea |
4.7 |
4.3 |
|
Respiratory tract infection |
2.3 |
4.3 |
3.1 |
Fatigue |
|
5.7 |
|
Nausea |
|
2.9 |
|
Abdominal pain |
|
1.4 |
|
Grade 4 TEAE, % |
|
|
|
Thrombocytopenia |
|
1.4 |
3.1 |
Anemia |
|
1.4 |
1.6 |
Respiratory tract infection |
|
|
1.6 |
Grade 5 TEAE, % |
|
|
|
Acute kidney injury |
|
0.7 |
|
Traumatic subdural hematoma |
|
0.7 |
|
Brain stem hemorrhage |
|
0.7 |
|
Disease progression |
|
0.7 |
|
Multiorgan failure due to sepsis |
|
|
1.3 |
Treatment discontinuation due to TEAE, % |
14.0 |
10.0 |
6.3 |
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