(An oncologist friend of mine said the Phase I results were the best he'd ever seen in pancreatic. Check out the slides.)
Clivatuzumab
Background
Clivatuzumab is a humanized monoclonal antibody targeting a mucin antigen expressed in most pancreatic cancers, but not pancreatitis, normal pancreas or most other normal tissues. The yttrium-90-labeled antibody has Orphan Drug status in both the United States and the European Union and fast track status in the U.S. for the treatment of pancreatic cancer.
Preclinical studies in mice with human pancreatic cancer xenografts given the murine version of Y-90 clivatuzumab tetraxetan demonstrated favorable tumor responses, which could be further improved when given in combination with gemcitabine. A prior Phase I single dose-escalation study of Y-90 clivatuzumab tetraxetan in treatment-relapsed pancreatic cancer patients has also produced encouraging results, with evidence of objective responses. Encouraging updated results from the current Phase Ib fractionated dose-escalation study of Y-90 clivatuzumab tetraxetan in combination with low-dose gemcitabine for the treatment of patients with newly diagnosed, inoperable, untreated, stage III or stage IV cancer of the pancreas were reported at the 2010 ASCO-GI Cancers symposium.
Clinical Study
Advanced Pancreatic Cancer
Our current study is a Phase Ib, open-label, dose-escalation of yttrium-90-labeled clivatuzumab tetraxetan administered as fractionated, multi-doses, in combination with low-dose gemcitabine, as frontline therapy for patients with Stage III or Stage IV metastatic pancreatic cancer. Updated results were presented at the 2010 ASCO-Gastrointestinal Cancers Symposium.
References
K. L. Pennington, M. J. Guarino, A. Sheikh, A. J. Ocean, A. N. Serafini, D. V. Gold, R. M. Sharkey, C. Rocha-Lima, K. Suppiah, C. J. Schneider, S. Garl, H. Horne, W. A. Wegener, D. M. Goldenberg. Repeated treatment cycles of fractionated radioimmunotherapy (RAIT) combined with low-dose radiosensitizing gemcitabine (GEM) in advanced pancreatic cancer. Amer. Soc. Clin. Oncol. 2010 Gastrointestinal Cancers Symposium Proceedings: 119, Abstract 247, (Board #A148), 2010.
D. V. Gold, M. Goggins, G. Newsome, D. E. Modrak, M. Liu, D. M. Goldenberg. The PAM4 serum enzyme immunoassay (EIA) for detection of early-stage pancreatic carcinoma. Amer. Soc. Clin. Oncol. 2010 Gastrointestinal Cancers Symposium Proceedings: 91, Abstract 135, (Board #A29), 2010.
K. Pennington, M. J. Guarino, A. N. Serafini, C. Rocha-Lima, K. Suppiah, C. J. Schneider, D. V. Gold, R. M. Sharkey, W. A. Wegener, D. M. Goldenberg. Multicenter study of radiosensitizing gemcitabine combined with fractionated radioimmunotherapy for repeated treatment cycles in advanced pancreatic cancer. J Clin Oncol 27:15s, 2009 (Suppl, abstr 4620).
S.A. Gulec, K. Pennington, D. Bruetman, S. Garl, H. Horne, D. Gold, W.Wegener, D.M. Goldenberg. A phase-I study of 90Y-hPAM4 (humanized anti-MUC1 monoclonal antibody) in patients with unresectable and metastatic pancreatic cancer. J Nucl Med. 48(Suppl, 2): 393P (Abstr.# 1664), 2007.
D.V. Gold, Z. Karanjawala, D.E. Modrak, D.M. Goldenberg, R.H. Hruban. PAM4-reactive MUC1 is a biomarker for early pancreatic adenocarcinoma. Clin Cancer Res. 13(24): 7380-7, 2007.
Bladerunner
AI
