90Y Clivatuzumab Tetraxetan
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 90Y 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 90Y Clivatuzumab tetraxetan in treatment-relapsed pancreatic cancer patients has also produced encouraging results, with evidence of objective responses.
Our current study is a Phase Ib/II fractionated dose-escalation trial of 90Y Clivatuzumab tetraxetan in combination with gemcitabine for the treatment of patients with newly diagnosed, inoperable, untreated, stage III or stage IV cancer of the pancreas. Final survival data from the first part of the trial, in which patients received 1 of 4 fractionated yttrium-90 doses and fixed low-dose gemcitabine, were reported at the 2011 annual meeting of the Society of Nuclear Medicine.
We expect to complete the Phase Ib/II study before the end of 2011 and provide an update at the 2012 Gastrointestinal Cancers Symposium. We plan to complete the final design of Phase III registration trial protocols, and begin clinical trials for this agent in 2012.
Advanced Pancreatic Cancer
Clivatuzumab tetraxetan is being evaluated as a frontline therapy for patients with advanced, inoperable pancreatic cancer. For more information on this clinical trial, please visit clinicaltrials.gov
Fractionated radioimmunotherapy with 90Y-Clivatuzumab tetraxetan (90Y-hPAM4) plus gemcitabine (Gem) in advanced pancreatic cancer (APC). S. Goldsmith, T. Manzone, M. Holt, A. Serafini, N. Hall, S.A. Gulec, N. Teoh, D.V. Gold, W.A. Wegener and D.M. Goldenberg. J Nucl Med 52 (Supplement 1):357, 2011.
Treatment of advanced pancreatic carcinoma with 90Y-Clivatuzumab tetraxetan: a phase I single-dose escalation trial. S.A. Gulec, S.J. Cohen, K.L. Pennington, L.S. Zuckier, R.J. Hauke, H. Horne, W.A. Wegener, N. Teoh, D.V. Gold, R.M. Sharkey, D.M. Goldenberg. Clin Cancer Res 17:4091-4100, 2011.
Activity of fractionated radioimmunotherapy with Clivatuzumab tetraxetan combined with low-dose gemcitabine (Gem) in advanced pancreatic cancer (APC). A.J. Ocean, M.J. Guarino, K.L. Pennington, A.J. Montero, T. Bekaii-Saab, S.A. Gulec, N. Teoh, D.V. Gold, W.A. Wegener, D.M. Goldenberg. J Clin Oncol 29 (suppl 4; abstr 240), 2011.
Detection of early-stage pancreatic adenocarcinoma. D.V. Gold, M. Goggins, D.E. Modrak, G. Newsome, M. Liu, C. Shi, R.H. Hruban, D.M. Goldenberg. Cancer Epidemiol Biomarkers Prev 19: 2786-2794, 2010.
Therapeutic effects of fractionated radioimmunotherapy (RAIT) with Clivatuzumab tetraxetan combined with low-dose gemcitabine (Gem) in advanced pancreatic cancer (APC). A.J. Ocean, M.J. Guarino, K.L. Pennington, B.H. O'Neil, C.S. Rocha Lima, T.S. Bekaii-Saab, S.A. Gulec, D.V. Gold, W.A. Wegener, D.M. Goldenberg. J Clin Oncol 28:15s (suppl; abstr 4115), 2010.
Repeated treatment cycles of fractionated radioimmunotherapy (RAIT) combined with low-dose radiosensitizing gemcitabine (GEM) in advanced pancreatic cancer. 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. Amer. Soc. Clin. Oncol. 2010 Gastrointestinal Cancers Symposium Proceedings: 119, Abstract 247, (Board #A148), 2010.
The PAM4 serum enzyme immunoassay (EIA) for detection of early-stage pancreatic carcinoma. D.V. Gold, M. Goggins, G. Newsome, D.E. Modrak, M. Liu, D.M. Goldenberg. Amer. Soc. Clin. Oncol. 2010 Gastrointestinal Cancers Symposium Proceedings: 91, Abstract 135, (Board #A29), 2010.
Multicenter study of radiosensitizing gemcitabine combined with fractionated radioimmunotherapy for repeated treatment cycles in advanced pancreatic cancer. 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. J Clin Oncol 27:15s (suppl; abstr 4620), 2009.
PAM4-reactive MUC1 is a biomarker for early pancreatic adenocarcinoma. D.V. Gold, Z. Karanjawala, D.E. Modrak, D.M. Goldenberg, R.H. Hruban. Clin Cancer Res 13:7380-7387, 2007.