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Picozzi VJ , Ramanathan RK , Lowery MA , Ocean AJ , Mitchel EP , O'Neil BH , Guarino MJ , Conkling PR , Cohen SJ , Bahary N , Frank RC , Dragovich T , Bridges BB , Braiteh FS , Starodub AN , Lee FC , Gribbin TE , Richards DA , Lee M , Korn RL , Pandit-Taskar N , Goldsmith SJ , Intenzo CM , Sheikh A , Manzone TC , Horne H , Sharkey RM , Wegener WA , O'Reilly EM , Goldenberg DM , Von Hoff DD
Y-clivatuzumab tetraxetan with or without low-dose gemcitabine: A phase Ib study in patients with metastatic pancreatic cancer after two or more prior therapies
Eur J Cancer. 2015 Sep;51(14) :1857-64
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BACKGROUND: For patients with metastatic pancreatic adenocarcinoma, there are no approved or established treatments beyond the 2nd line. A Phase Ib study of fractionated radioimmunotherapy was undertaken in this setting, administering 90Y-clivatuzumab tetraxetan (yttrium-90-radiolabelled humanised antibody targeting pancreatic adenocarcinoma mucin) with or without low radiosensitising doses of gemcitabine. METHODS: Fifty-eight patients with three (2-7) median prior treatments were treated on Arm A (N=29, 90Y-clivatuzumab tetraxetan, weekly 6.5mCi/m2dosesx3, plus gemcitabine, weekly 200mg/m2 dosesx4 starting 1week earlier) or Arm B (N=29, 90Y-clivatuzumab tetraxetan alone, weekly 6.5mCi/m2dosesx3), repeating cycles after 4-week delays. Safety was the primary endpoint; efficacy was also evaluated. RESULTS: Cytopaenias (predominantly transient thrombocytopenia) were the only significant toxicities. Fifty-three patients (27 Arm A, 26 Arm B, 91% overall) completed 1 full treatment cycles, with 23 (12 Arm A, 11 Arm B; 40%) receiving multiple cycles, including seven (6 Arm A, 1 Arm B; 12%) given 3-9 cycles. Two patients in Arm A had partial responses by RECIST criteria. Kaplan-Meier overall survival (OS) appeared improved in Arm A versus B (hazard ratio [HR] 0.55, 95% CI: 0.29-0.86; P=0.017, log-rank) and the median OS for Arm A versus Arm B increased to 7.9 versus 3.4months with multiple cycles (HR 0.32, P=0.004), including three patients in Arm A surviving >1year. CONCLUSIONS: Clinical studies of 90Y-clivatuzumab tetraxetan combined with low-dose gemcitabine appear feasible in metastatic pancreatic cancer patients beyond 2nd line and a Phase III trial of this combination is now underway in this setting.
Picozzi, Vincent J Ramanathan, Ramesh K Lowery, Maeve A Ocean, Allyson J Mitchel, Edith P O'Neil, Bert H Guarino, Michael J Conkling, Paul R Cohen, Steven J Bahary, Nathan Frank, Richard C Dragovich, Tomislav Bridges, Benjamin B Braiteh, Fadi S Starodub, Alexander N Lee, Fa-Chyi Gribbin, Thomas E Richards, Donald A Lee, Marie Korn, Ronald L Pandit-Taskar, Neeta Goldsmith, Stanley J Intenzo, Charles M Sheikh, Arif Manzone, Timothy C Horne, Heather Sharkey, Robert M Wegener, William A O'Reilly, Eileen M Goldenberg, David M Von Hoff, Daniel D P30 CA008748/CA/NCI NIH HHS/ Eur J Cancer. 2015 Sep;51(14):1857-64. doi: 10.1016/j.ejca.2015.06.119. Epub 2015 Jul 14.