1. PERSIST-1: Pacritinib Improved Spleen Volume Reductions in Myelofibrosis vs Best Available Therapy CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting*
May 29 - June 2, 2015
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
This program is supported by educational grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene Corporation, Genentech, Incyte, and Novartis.

2. Myelofibrosis and JAK Inhibition
Myelofibrosis: rare hematologic malignancy that is associated with poor prognosis and pt quality of life[1-3]
Disease-related thrombocytopenia, anemia, and red blood cell transfusion increase within 1 yr of diagnosis[4]
Thrombocytopenia is a negative prognostic factor for OS[5]
Associated with risk of leukemic transformation[5]
Medical need to develop therapies that can simultaneously alleviate symptoms, splenomegaly, and cytopenias in pts with myelofibrosis
Pacritinib, a selective JAK2/FLT3 inhibitor, showed positive efficacy in phase II trial and favorable safety profile in phase I studies[6,7]
Current phase III study evaluated pacritinib vs best available therapy in pts with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV- MF, or post-essential thrombocythemia-myelofibrosis (PET-MF)[8]
OS, overall survival.
1. Tefferi A, et al. Blood. 2013;122: Mesa RA, et al. Cancer. 2007;109: Geyer HL, et al. Blood. 2014;124: Tefferi A, et al. Mayo Clin Proc. 2012;87: Gangat N, et al. J Clin Oncol. 2010;29: Seymour F, et al. Blood. 2010; 95:Abstract Komrokji RS, et al. Blood. 2015;125: Mesa RA, et al. ASCO Abstract LBA7006.

3. PERSIST-1: Study Design
Randomized phase III study
Primary endpoint: proportion of pts achieving a ≥ 35% reduction in spleen volume (by MRI/CT) from baseline to Wk 24
Stratified by platelet count (< 100,000/µL vs < 50,000/µL), risk category, region
Wk 24
Pts with intermediate- or high-risk myelofibrosis, palpable spleen ≥ 5 cm, and no previous treatment with JAK2 inhibitors
(N = 327)
Pacritinib 400 mg/day
(n = 220)
Best Available Therapy*
(n = 107)
CT, computed tomography; MRI, magnetic resonance imaging.
*Ruxolitinib excluded. Best available therapies included hydroxyurea, glucocorticoids, erythropoiesis-stimulating agents, immunomodulatory agents, mercaptopurine, danazol, interferons, cytarabine, melphalan.
Mesa RA, et al. ASCO Abstract LBA7006. Reprinted with permission.

4. PERSIST-1: Baseline Characteristics
Pacritinib
(n = 220)
Best Available Therapy
(n = 107)
Median age, yrs (range)
≥ 65 yes, n (%)
67 (23-87)
135 (61)
65 (37-84)
55 (51)
Male, n (%)
125 (57)
60 (56)
Median spleen length by physical exam, cm (range)
12 (4-33)
(n = 219)
12 (4-30)
(n = 106)
Median spleen volume by MRI/CT, cm3 (range)
2223 ( )
(n = 218)
2367 ( )
IPSS score, n (%)
Int-1
Int-2
High
Missing
30 (14)
76 (35)
106 (48)
8 (4)
18 (17)
35 (33)
51 (48)
3 (3)
ECOG PS, n (%)
0-1
2-3
191 (87)
29 (13)
96 (90)
11 (10)
JAK2V617F positive, n (%)
154 (70)
92 (86)
CT, computed tomography; ECOG PS, Eastern Cooperative Oncology Group performance status; Int, intermediate; IPSS, International Prognostic Scoring System; JAK, Janus kinase; MRI, magnetic resonance imaging.
Mesa RA, et al. ASCO Abstract LBA7006. Reprinted with permission.

5. PERSIST-1: Reduction of Spleen Volume ≥ 35% at Wk 24
Significantly greater percentage of pts in the pacritinib arm reached the primary endpoint 60
Pacritinib (n = 168)
Best available therapy (n = 85) 50 40 30 20 10
-10
Change From Baseline (%)
-20
-30
BAT, best available therapy; CT, computed tomography; ITT, intent to treat; MRI, magnetic resonance imaging; PAC, pacritinib.
35% decrease
-40
-50
Pts Reaching Primary Endpoint, %
Population
PAC
BAT
P Value
ITT
19.1
4.7
.0003
Evaluable*
25.0
5.9
.0001
-60
-70
-80
-90
-100
Patients
Mesa RA, et al. ASCO Abstract LBA7006. Reprinted with permission.
*Baseline + Wk 24 spleen assessment by MRI or CT.

6. PERSIST-1: Primary Endpoint Subanalyses
Correlation of Spleen Volume Reduction With OS
Spleen Volume Reduction
HRb (95% CI)
P Value
PAC
10% to < 20%
≥ 20%
0.15 ( )
0.26 ( )
.071
.014
BAT
2.31 ( ) NA
.0287
P=.0370
35%
33.3%
PAC
BAT
P=.0072
30%
P=.0451
23.5%
25%
22.9%
P=.0086
20%
16.7%
Patients
15%
10% 5% 0% 0% 0% 0% 0%
ITT
Evaluablea
ITT
Evaluablea
BAT, best available therapy; ITT, intent to treat; NA, not applicable; OS, overall survival; PAC, pacritinib.
Significant percentage of pts in the pacritinib arm reached the primary endpoint regardless of baseline thrombocytopenia
Spleen volume reduction ≥ 20% at Wk 24 significantly associated with OS
aBaseline + Wk 24 spleen assessment by MRI or CT.
bReference: < 10% spleen volume reduction.
Mesa RA, et al. ASCO Abstract LBA7006. Reprinted with permission.

7. PERSIST-1 Secondary Endpoint: Reduction in Total Symptom Score
PAC
BAT
PAC
BAT
P<.0001
16.7%
41.9%
P=.790
<100,000µL
7.5%
40.4%
P<.0001
≥100,000µL
P<.0001
8.8%
25.0%
P=.0677
<100,000µL
30%
5.5%
24.3%
P=.0004
<100,000µL
45%
40.9%
6.3%
20.0%
P=.4086
<50,000µL
40%
11.1%
31.8%
P=.3791
<50,000µL
35%
24.5%
35%
20%
30%
25%
Patients
15%
20%
10%
15%
6.5%
9.9%
10% 5% 5% 0% 0%
ITT
Evaluable Population
BAT, best available therapy; ITT, intent to treat; PAC, pacritinib
Platelet Subgroup
Platelet Subgroup
Significantly greater percentage of pts in the PAC arm achieved ≥ 50% reduction in total symptom score at Wk 24
In evaluable population, proportion achieving this endpoint with PAC increased over 24 wks
Mesa RA, et al. ASCO Abstract LBA7006. Reprinted with permission.

8. PERSIST-1: Adverse Events
Most common adverse events: diarrhea, nausea, vomiting
Grade 3/4 GI events higher in PAC arm than BAT
Clinical benefit of pacritinib preserved regardless of any GI adverse event
More frequent in pts aged older than 65 yrs and in pts with platelets < 100,000/μL
Diarrhea resulted in discontinuation or dose interruption in 3 and 13 pts, respectively
Blood and lymphatic system disorders similar between arms
Adverse GI Event, n (%)
All Grades
Grade 3
Grade 4
PAC
(n = 220)
BAT
(n = 106)
Diarrhea
117 (53.2)
13 (12.3)
11 (5.0)
Nausea
59 (26.8)
7 (6.6)
2 (0.9)
Vomiting
35 (15.9)
6 (5.7)
BAT, best available therapy; GI, gastrointestinal; PAC, pacritinib.
Mesa RA, et al. ASCO Abstract LBA7006. Reprinted with permission.

9. PERSIST-1: Investigator Conclusions
Pacritinib associated with
Significantly more pts reaching primary endpoint (≥ 35% reduction of spleen volume), regardless of baseline platelet count (P = .0003)
At Wk 24 demonstrated significant improvement of HR of survival for pts with ≥ 20% SVR (HR: 0.26; 95% CI: ; P = .014)
Significant treatment effect in pts with baseline platelets < 50,000/μL (highest risk subset; P < .05)
In this subset, 35% achieved mean increase in platelet counts by Wk 24
Significant reduction in total symptom score (P < .0001)
Significantly higher proportion of pts developed RBC-transfusion independence
Based on preliminary data, additional studies of pacritinib in combination with other potentially disease-modifying agents are warranted in pts with myelofibrosis
SVR, spleen volume reduction; RBC, red blood cell.
Mesa RA, et al. ASCO Abstract LBA7006.

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