1. Phase II HALO-202: nab-Paclitaxel and Gemcitabine ± PEGPH20 in Untreated Metastatic Pancreatic Ductal Adenocarcinoma
CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois
*Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals
This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

2. nab-Paclitaxel/Gemcitabine ± PEGPH20 in Untreated Pancreatic Cancer: Background
Accumulation of hyaluronan associated with accelerated tumor growth, negative predictor of survival in pancreatic ductal adenocarcinoma
Naturally occurring polysaccharide component of tumor stroma
Increases interstitial pressure, restricts blood flow and potentially drug delivery
PEGPH20 (pegvorhyaluronidase alfa): degrades hyaluronan, remodels stroma
HALO-202: phase II trial evaluating efficacy, safety of adding PEGPH20 to nab-paclitaxel + gemcitabine in previously untreated metastatic pancreatic ductal adenocarcinoma
Slide credit: clinicaloptions.com
Hingorani SR, et al. ASCO Abstract 4008.

3. HALO-202: Phase II Study Design
Stage 1 (n = 146)
1:1 randomization
Clinical hold set due to increased TE events in PAG arm
Training Set for HA assay
PEGPH20 3 mg/kg IV 2/wk x 3 wks cycle 1
then 1/wk x 3 wks cycle 2+ +
nab-Paclitaxel 125 mg/m2 Days 1, 8, 15 +
Gemcitabine 1000 mg/m2 Days 1, 8, 15
(n = 166)
Pts with previously untreated stage IV
pancreatic ductal adenocarcinoma;
KPS
(N = 279)
nab-Paclitaxel 125 mg/m2 Days 1, 8, 15 +
Gemcitabine 1000 mg/m2 Days 1, 8, 15
(n = 113)
Stage 2 (n = 133)
2:1 randomization
Protocol amendment to include TE screening and enoxaparin prophylaxis
Validation Set to evaluate HA algorithm
DCR, disease control rate; DoR, duration of response; HA, hyaluronan; ITT, intent to treat; KPS, Karnofsky performance status; PAG, PEGPH20 + nab-paclitaxel + gemcitabine; TE, thromboembolic event.
Endpoints
Primary: PFS, thromboembolic event rate
Secondary: PFS by HA level, ORR, OS
Exploratory: OS by HA level, DoR, DCR
Analysis Populations
ITT: baseline, efficacy
Treated: safety
Slide credit: clinicaloptions.com
Hingorani SR, et al. ASCO Abstract 4008.

4. HALO-202: Pt Characteristics (Stages 1 + 2)
All Pts
HA High*
PAG
(n = 166) AG
(n = 113)
(n = 49)
(n = 35)
Mean age, yrs (SD)
≥ 65 yrs, %
64 (10) 53
65 (9) 55
66 (9) 67
67 (7) 63
Male, % 61 49 43
KPS 70-80/≥ 90, %
32/68
36/64
33/67
37/63
Primary tumor location, %
Head
Body
Tail 38 19 35 51 12 25 47 29 57 11
Metastasis in liver/lung, %
92/26
86/27
90/33
74/31
Serum CA 19-9 ≥ 37 U/mL, % 84 82 80 86
AG, nab-paclitaxel + gemcitabine; CA, calcium; ECM, extracellular matrix; HA, hyaluronan; KPS, Karnofsky performance status; PAG, PEGPH20 + nab-paclitaxel + gemcitabine; SD, standard deviation
*HA high defined as ≥ 50% of ECM stained for hyaluronan using HA RxDx assay
Slide credit: clinicaloptions.com
Hingorani SR, et al. ASCO Abstract Pu J, et al. ASCO Abstract e23196.

5. HALO-202: PFS (Stages 1 + 2) All Pts HA-High Subset 100 100 PAG AG PAG
(n = 166)
102
6.0 AG
(n = 113) 67
5.3
100
100
Events
Median PFS, mo
HR (95% CI)
P value
PAG
(n = 49) 24
9.2 AG
(n = 35) 19
5.2
0.51 ( )
.048
PAG AG
PAG AG
Events
Median PFS, mo
HR (95% CI)
P value 80 80
0.73 ( )
.045 60 60
PFS (%)
PFS (%) 40 40 20 20
AG, nab-paclitaxel + gemcitabine; HA, hyaluronan; PAG, PEGPH20 + nab-paclitaxel + gemcitabine 2 4 6 8 10 12 14 16 18 2 4 6 8 10 12 14 16 18
Pts at Risk, n
PAG AG
Mos
Pts at Risk, n
PAG AG
Mos
166
113
101 62 79 42 55 26 36 9 22 4 9 2 7 1
166
113
101 62 79 42 55 26 36 9 22 4 9 2 7 1
Slide credit: clinicaloptions.com
Hingorani SR, et al. ASCO Abstract Reproduced with permission.

6. HALO-202: Other Efficacy Outcomes
All Pts
HA-High
PAG
(n = 166) AG
(n = 113)
(n = 49)
(n = 35)
Stages 1 + 2
ORR, % 40 33 45 31
Median OS, mos NR
11.5
8.5
HR (95% CI)
0.96 ( )
Stage 2 only
Median PFS, mos
8.6
4.5
0.63 ( )
11.7
7.8
0.52 ( )
AG, nab-paclitaxel + gemcitabine; HA, hyaluronan; NR, not reported; PAG, PEGPH20 + nab-paclitaxel + gemcitabine.
Slide credit: clinicaloptions.com
Hingorani SR, et al. ASCO Abstract 4008.

7. HALO-202: Thromboembolic Events
No difference in TE rate by treatment arm or tumor HA level
TE Rate, % (n/N)
All Pts
PAG
(n = 166) AG
(n = 113)
Stage 1
43 (32/74)
25 (15/61)
Stage 2
40 mg/day enoxaparin*
1 mg/kg/day enoxaparin*
14 (12/86)
28 (5/18)
10 (7/68)
10 (4/39)
29 (2/7)
6 (2/32)
*Prophylaxis.
AG, nab-paclitaxel + gemcitabine; HA, hyaluronan; PAG, PEGPH20 + nab-paclitaxel + gemcitabine; TE, thromboembolic event.
Slide credit: clinicaloptions.com
Hingorani SR, et al. ASCO Abstract 4008.

8. HALO-202: Treatment-Related Adverse Events
Selected Adverse Event in ≥ 25% of Pts, %
PAG
(n = 160) AG
(n = 100)
Any Grade
Grade ≥ 3
Fatigue 72 21 66 16
Peripheral edema 63 5 26 4
Muscle spasms 56 13 3 1
Diarrhea 40 7 39
Anemia 17 38 20
Neutropenia 34 29 19 18
Peripheral neuropathy 6 31 8
Myalgia
Thrombocytopenia 9
AG, nab-paclitaxel + gemcitabine; PAG, PEGPH20 + nab-paclitaxel + gemcitabine.
Slide credit: clinicaloptions.com
Hingorani SR, et al. ASCO Abstract 4008.

9. HALO-202: Conclusions
Addition of PEGPH20 to nab-paclitaxel + gemcitabine improved PFS in both full study population and subgroup with high tumor HA
Trend toward improved OS in Stage 2 HA-high pts
Protocol amendments including TE screening and use of LMWH prophylaxis reduced TE events
Safety profile of combination regimen manageable
Investigators conclude data support ongoing randomized phase III multicenter HALO-301 study of PEGPH20 + nab-paclitaxel + gemcitabine in pts with stage IV pancreatic ductal adenocarcinoma and high HA levels
HA, hyaluronan; LMWH, low-molecular-weight heparin; TE, thromboembolic event.
Slide credit: clinicaloptions.com
Hingorani SR, et al. ASCO Abstract 4008.

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