1. Results of a Randomized Phase III Trial (MPACT) of Weekly nab-Paclitaxel Plus
Gemcitabine vs Gemcitabine Alone for Patients With Metastatic Adenocarcinoma of the Pancreas With PET and CA19-9 Correlates
Daniel D. Von Hoff,1 Thomas Ervin,2 Francis P. Arena,3 E. Gabriela Chiorean,4 Jeffrey Infante,5 Malcolm Moore,6 Thomas Seay,7 Sergey A. Tjulandin,8 WenWee Ma,9 Mansoor N. Saleh,10 Marion Harris,11 Michele Reni,12 Ramesh K. Ramanathan,1 Josep Tabernero,13 Manuel Hidalgo,14 Eric Van Cutsem,15 David Goldstein,16 Xinyu Wei,17 Jose Iglesias,18 Markus F. Renschler 17
1TGen, Scottsdale Healthcare, AZ, USA; 2Florida Cancer Specialists/Sarah Cannon Research Institute, Englewood, FL; 3Arena Oncology Associates, Lake Success, NY, USA; 4University of Washington, Seattle, WA, USA; 5Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN; 6Princess Margaret Hospital, Toronto, Canada; 7Atlanta Cancer Care, GA, USA; 8Blokhin Cancer Research Center, Moscow, Russia; 9Roswell Park Cancer Institute, Buffalo, NY, USA; 10Cancer Specialists, Atlanta, GA, USA; 11Southern Health, East Bentleigh, VIC, Australia; 12San Raffaele Scientific Institute, Milan, Italy; 13Vall d'Hebron University Hospital, Barcelona, Spain; 14Centro Integral Oncológico Clara Campal, Madrid, Spain; 15Leuven University, Belgium; 16Prince of Wales Hospital, Sydney, NSW, Australia; 17Celgene Corporation, Summit, NJ, USA; 18Bionomics, Thebarton, Australia

2. Disclosures
This study was sponsored by Celgene Corporation Von Hoff: consultant or advisory role, honoraria, and research funding, Celgene; Ervin: research funding, Celgene; Arena: research funding, Clinical Research Alliance and Celgene; Chiorean: research funding, Celgene; Moore: consultant or advisory role and research funding, Celgene; Seay: research funding, Celgene; Tjulandin: research funding, Celgene; Ma: research funding, Celgene; Saleh: research funding, Celgene; Reni: consultant or advisory role, honoraria, and research funding, Celgene; Ramanathan: consultant or advisory role, honoraria, and research funding, Celgene; Tabernero: consultant or advisory role and honoraria, Celgene; Hidalgo: consultant or advisory role, honoraria, and research funding, Celgene; Van Cutsem: research funding, Celgene; Goldstein: consultant or advisory role and research funding, Celgene; Wei: employment or leadership position and stock ownership, Celgene; Iglesias: employment or leadership position at Bionomics and stock ownership, Celgene; Renschler: employment or leadership position and stock ownership, Celgene; Infante, Harris: nothing to disclose.
Von Hoff et al. ASCO 2013. 2

3. nab-Paclitaxel + Gemcitabine
in Pancreatic Cancer
1. Preclinical models1,2:
nab-Paclitaxel (nab-P) active as single agent
Synergizes with gemcitabine (Gem)
2. In a 67-patient phase I/II trial of nab-P + Gem1
MTD: nab-P 125 mg/m2 + Gem 1000 mg/m2 on days 1, 8, and 15 every 28 days
Promising activity at MTD
ORR: 48%
Median PFS: 7.9 months
Median OS: 12.2 months
Von Hoff DD, et al. J Clin Oncol. 2011;29:
Frese KK, et al. Cancer Discov. 2012;2:
Von Hoff et al. ASCO 2013. 3

4. Study Design nab-P Planned N = 842 Gem Gem
125 mg/m2 IV qw 3/4 +
Gem
1000 mg/m2 IV qw 3/4
Planned N = 842
Stage IV
No prior treatment for metastatic disease
KPS ≥ 70
Measurable disease
Total bilirubin ≤ ULN
No age limitation
1:1, stratified by KPS, region, liver metastasis
Gem
1000 mg/m2 IV qw 7/8
then qw 3/4
Primary endpoint OS
Secondary endpoints
PFS and ORR by independent review (RECIST)
Safety and tolerability
By NCI CTCAE v3.0
With 608 events, 90% power to detect OS; HR = (2-sided α = 0.049)
Treat until progression
CT scans every 8 weeks
PET scans in an initial cohort of patients at baseline and weeks 8 and 16
CA19-9 measurements at baseline and every 8 weeks
Von Hoff et al. ASCO 2013. 4

5. MPACT (CA046) Phase III Trial
Country
nab-P + Gem, n
Gem, n
All, n (%)
USA
235
241
476 (55)
Australia 61 59
120 (14)
Russia 50
100 (12)
Canada 33 30
63 (7)
Italy 21 16
37 (4)
Ukraine 14 12
26 (3)
Spain 6 10
16 (2)
Germany 3 5
8 (1)
Austria
6 (1)
France 4 2
Belgium 1
3 (< 1)
Total
431
430
861 (100)
Table Demographic and Baseline Characteristics - Intent-to-Treat Population
Total of 151 sites enrolled 861 patients between May 8, 2009, and April 17, 2012
Von Hoff et al. ASCO 2013. 5

6. Baseline Characteristics
Variable
nab-P + Gem (n = 431)
Gem
(n = 430)
All Patients
(N = 861)
Age
Median years (min, max)
62 (27, 86)
63 (32, 88)
63 (27, 88)
≥ 65 years old, % 41 44 42
Sex
Male, % 57 60 58
KPS
90-100, % 62
70-80, % 38 40
Pancreatic primary location
Head, % 43
Body, % 31 32
Tail, % 24 26 25
Current site(s) of metastasis
Lung, % 35 39
Liver, % 85 84
No. of metastatic sites
1, % 8 5 6
2, % 47 48
≥ 3, % 45 46
Previous Whipple
Yes, % 7
Biliary stent 19 16 17
CA19-9a
Normal, % 14 13
> ULN-< 59 ×ULN, % 28
≥ 59 × ULN, %
ULN, upper limit of normal.
a CA19-9 at baseline was unknown in 13% of patients.
Table Demographic and Baseline Characteristics, Intent-to-Treat Population
Table Cancer History
Von Hoff et al. ASCO 2013. 6

7. Proportion of Survival
Overall Survival
1.0
OS, months
Events/n (%)
Median (95% CI)
75th Percentile
333/431 (77)
8.5 ( )
14.8
359/430 (83)
6.7 ( )
11.4
0.9
0.8
nab-P + Gem
Gem
0.7
0.6
Proportion of Survival
0.5
0.4
HR = 0.72
95% CI ( )
P =
0.3
0.2
0.1
Table Overall Survival –Stratified Analysis by Randomization Strata, Intent-to-Treat Population
0.0 3 6 9 12 15 18 21 24 27 30 33 36 39
Months
Pts at risk
nab-P + Gem:
Gem:
431
430
357
340
269
220
169
124
108 69 67 40 26 27 15 16 7 9 3 4 1
Subsequent therapy: 38% for nab-P + Gem and 42% for Gem
OS censored at time of secondary therapy: 9.4 vs 6.8 months; HR 0.68; P =
Trial conclusions not impacted by secondary therapies
Von Hoff et al. ASCO 2013. 7

8. Overall Survival Rate nab-P + Gem Gem Time Points, months Survival, %
Increase, %
P Value 6 67 55 22 9 48 36 33 12 35 59 18 16 78 24 4
125
Table Overall Survival –Stratified Analysis by Randomization Strata, Intent-to-Treat Population
Von Hoff et al. ASCO 2013. 8

9. OS—Prespecified Subgroups
nab-P + Gem
Events/n
Gem HR
333/431
359/430
0.72
188/254
209/242
0.65
145/177
150/188
0.81
138/186
141/173
195/245
218/257
142/179
146/161
0.61
187/248
212/268
0.75
142/191
155/180
0.59
188/237
201/246
0.80
290/365
309/360
0.69
43/66
50/70
0.86
21/33
16/21
0.41
159/202
163/206
104/136
121/140
0.79
49/60
59/63
0.50
47/60
43/56
1.07
96/122
95/120
0.83
151/197
171/195
50/61
53/59
0.67
62/64
59/62
0.84
14/38
17/38
207/268
230/271
0.68
Group HR
All patients
Age < 65 years
Age ≥ 65 years
Female
Male
KPS 70-80
KPS
Primary tumor location: head
Primary tumor location: other
No liver metastases
Liver metastases
Normal CA19-9
CA19-9 ULN to < 59 x ULN
CA19-9 ≥ 59 x ULN
> 3 metastatic sites
1 metastatic site
3 metastatic sites
2 metastatic sites
Will be redone with log scale
Australia
Western Europe
North America
Eastern Europe
0.125
0.25
0.5
1.0
2.0
Favors nab-P + Gem
Favors Gem
Von Hoff et al. ASCO 2013. 9

10. PFS by Independent Review Proportion of Progression-Free Survival
PFS, months
Events/n (%)
Median (95% CI)
75th Percentile
277/431 (64)
5.5 ( )
9.2
265/430 (62)
3.7 ( )
5.9
1.0
0.9
0.8
nab-P + Gem
Gem
0.7
0.6
Proportion of Progression-Free Survival
0.5
HR = 0.69
95% CI ( )
P =
0.4
0.3
0.2
0.1
0.0 3 6 9 12 15 18 21 24
Pts at Risk
nab-P + Gem:
Gem:
431
430
281
209
122 51 62 23 24 10 8 6 4 2
Months
PFS Rate at
nab-P + Gem
Gem
Increase
6 months
44%
25%
76%
12 months
16% 9%
78%
Von Hoff et al. ASCO 2013. 10

11. Response Rates Variable nab-P + Gem (n = 431) Gem (n = 430) P Value
Overall response rate
Independent review, %
(95% CI)
Investigator assessment, % 23
( ) 29
( ) 7
( ) 8
( )
1.1 x 10−10
3.3 x 10−16
Disease control rate by independent review,a % 48
( ) 33
( )
7.2 x 10−6
Table Overall Response Rate by Independent Radiological Review, Intent-to-Treat Population
Table Overall Response Rate by Investigator Review, Intent-to-Treat Population
Table Disease Control Rate by Independent Radiological Review, Intent-to-Treat Population
a Includes CR + PR + SD ≥ 16 weeks.
Von Hoff et al. ASCO 2013. 11

12. Treatment Exposure Variable nab-P + Gem (n = 421) Gem (n = 402)
Treatment duration, median months (min, max)
≥ 6 months, %
3.9 (0.1, 21.9) 32
2.7 (0.1, 21.5) 15
Relative dose intensity (%), median (min, max)
nab-P
80.6 (16.7, 100.0)
75.2 (14.3, 97.7) --
84.6 (14.1, 100.0)
Cumulative dose, median mg/m²
1425.0
11,400.0
9000.0
nab-P doses at 125 mg/m², n (%)
Gem doses at 1000 mg/m², n (%)
(71)
(63)
(79)
Table
Table
Table
Von Hoff et al. ASCO 2013. 12

13. Safety Preferred Term nab-P + Gem (n = 421) Gem (n = 402)
Pts with at least 1 AE leading to death, % 4
Grade ≥ 3 hematologic AEs,a %
Neutropenia
Thrombocytopenia
Anemia 38 13 27 9 12
Pts who received growth factors, % 26 15
Febrile neutropenia,b % 3 1
Grade ≥ 3 nonhematologic AEsb in > 5% pts, %
Fatigue
Peripheral neuropathyc
Diarrhea 17 6 7
< 1
Grade ≥ 3 neuropathy
Time to onset, median days
Time to improvement by 1 grade, median days
Time to improvement to grade ≤ 1, median days
Pts who resumed nab-P, %
140 21 29 44
113 --
Hematologic values: table
Nonhematologic: table
Febrile neutropenia:
AE leading to death:
Neuropathy time: table
a Based on laboratory values; b Based on investigator assessment of treatment-related events; c Grouped term.
Von Hoff et al. ASCO 2013. 13

14. Metabolic Response by PET by Independent Review
PET scans were performed in the first 257 patients randomized to receive treatment at PET-equipped centers
Outcome
nab-P + Gem
(n = 130)a
Gem
(n = 127)a HR
P Value
Metabolic response by PET,b % 63 38 -
ORR by CT scan, % 31 11
0.0001
Median OS in PET cohort, mo
10.5
8.3
0.71
0.0096
a Follow-up scans at 8 weeks (n = 222) and 16 weeks (n = 134).
b PET evaluated by EORTC criteria (Young H, et al. Eur J Cancer. 1999;35: ).
Von Hoff et al. ASCO 2013. 14

15. CA19-9 Best Response and Landmark OS Analyses
Best Decrease in CA19-9 During Study
Decrease in CA19-9 level
nab-P + Gem
(n = 379)
Gem
(n = 371)
P Value
Patients with a ≥ 20% decrease, n (%)
230 (61)
162 (44)
<
Patients with a ≥ 90% decrease, n (%)
117 (31)
51 (14)
Predictive Value of CA19-9 Response at Week 8 on OS: Landmark Analyses
Decrease in CA19-9 Level at Week 8 HR n
Median OS, mo
≥ 20%
197
13.2
141
9.4
0.59
≥ 90% 59
13.4 34
9.8
0.47
0.0053
Detailed analysis presented by Chiorean et al. (abstract 4058)
Von Hoff et al. ASCO 2013. 15

16. Conclusions from MPACT
MPACT study – a large, multi-center, international study performed at community and academic centers
OS, PFS, and ORR were superior for nab-P + Gem vs Gem
Improvement in OS across the entire curve, including median, 1-year, and 2-year survival rates
Metabolic response rate by PET and CA19-9 response rates were higher for nab-P + Gem vs Gem alone
Both were predictors for longer OS
Von Hoff et al., ASCO 2013 16

17. Conclusions from MPACT (cont)
Serious life threatening toxicity not increased; AEs acceptable and manageable
5. nab-P + Gem, a new standard for the treatment of patients with metastatic pancreatic cancer, is superior to Gem alone and could become the backbone for new regimens
A phase III study of nab-P + Gem in the adjuvant setting is currently in development
Von Hoff et al., ASCO 2013 17

18. MPACT Team
Von Hoff et al. ASCO 2013. 18