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Results of a Randomized Phase III Trial (MPACT) of Weekly nab -Paclitaxel Plus

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.

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Results of a Randomized Phase III Trial (MPACT) of Weekly nab -Paclitaxel Plus

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  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,8WenWee 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. 2 Von Hoff et al. ASCO 2013.

  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 ClinOncol. 2011;29:4548-4554. Frese KK, et al. Cancer Discov. 2012;2:260-269. 3 Von Hoff et al. ASCO 2013.

  4. Study Design nab-P 125 mg/m2IV 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 • PFSand ORR by independent review (RECIST) • Safety and tolerability • By NCI CTCAE v3.0 • With 608 events, 90% power to detect OS; HR = 0.769 (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 4 Von Hoff et al. ASCO 2013.

  5. MPACT (CA046) Phase III Trial Total of 151 sites enrolled 861 patients between May 8, 2009, and April 17, 2012 5 Von Hoff et al. ASCO 2013.

  6. Baseline Characteristics 6 Von Hoff et al. ASCO 2013.

  7. Overall Survival 1.0 0.9 0.8 nab-P + Gem 0.7 Gem 0.6 0.5 Proportion of Survival 0.4 HR = 0.72 95% CI (0.617-0.835) P= 0.000015 0.3 0.2 0.1 0.0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 Months Pts at risk nab-P + Gem: 431 357 269 169 108 67 40 27 16 9 4 1 1 0 Gem: 430 340 220 124 69 40 26 15 7 3 1 0 0 0 • 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 = 0.00007 • Trial conclusions not impacted by secondary therapies 7 Von Hoff et al. ASCO 2013.

  8. Overall Survival Rate 8 Von Hoff et al. ASCO 2013.

  9. OS—Prespecified Subgroups Group HR All patients Age < 65 years Age ≥ 65 years Female Male KPS 70-80 KPS 90-100 Australia Eastern Europe Western Europe North America Primary tumor location: head Primary tumor location: other Liver metastases No liver metastases 1metastatic site 2metastatic sites 3 metastatic sites > 3 metastatic sites Normal CA19-9 CA19-9 ULN to < 59 x ULN CA19-9 ≥ 59 x ULN 1.0 0.125 0.25 0.5 2.0 9 Von Hoff et al. ASCO 2013. Favors nab-P + Gem Favors Gem

  10. PFS by Independent Review 1.0 0.9 0.8 nab-P + Gem 0.7 Gem 0.6 Proportion of Progression-Free Survival 0.5 HR = 0.69 95% CI (0.581-0.821) P = 0.000024 0.4 0.3 0.2 0.1 0.0 0 3 6 9 12 15 18 21 24 Months Pts at Risk nab-P + Gem: 431 281 122 62 24 8 4 2 0 Gem: 430 209 51 23 10 6 4 0 0 Von Hoff et al. ASCO 2013. 10

  11. Response Rates a Includes CR + PR + SD ≥ 16 weeks. 11 Von Hoff et al. ASCO 2013.

  12. Treatment Exposure 12 Von Hoff et al. ASCO 2013.

  13. Safety a Based on laboratory values; b Based on investigator assessment of treatment-related events; c Grouped term. 13 Von Hoff et al. ASCO 2013.

  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 14 Von Hoff et al. ASCO 2013.

  15. CA19-9 Best Response and Landmark OS Analyses Detailed analysis presented by Chiorean et al. (abstract 4058) 15 Von Hoff et al. ASCO 2013.

  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 16 Von Hoff et al., ASCO 2013

  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 17 Von Hoff et al., ASCO 2013

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

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