(90)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
Vincent J Picozzi, Ramesh K Ramanathan, Maeve A Lowery, Allyson J Ocean, Edith P Mitchel, Bert H O'Neil, Michael J Guarino, Paul R Conkling, Steven J Cohen, Nathan Bahary, Richard C Frank, Tomislav Dragovich, Benjamin B Bridges, Fadi S Braiteh, Alexander N Starodub, Fa-Chyi Lee, Thomas E Gribbin, Donald A Richards, Marie Lee, Ronald L Korn, Neeta Pandit-Taskar, Stanley J Goldsmith, Charles M Intenzo, Arif Sheikh, Timothy C Manzone, Heather Horne, Robert M Sharkey, William A Wegener, Eileen M O'Reilly, David M Goldenberg, Daniel D Von Hoff, Vincent J Picozzi, Ramesh K Ramanathan, Maeve A Lowery, Allyson J Ocean, Edith P Mitchel, Bert H O'Neil, Michael J Guarino, Paul R Conkling, Steven J Cohen, Nathan Bahary, Richard C Frank, Tomislav Dragovich, Benjamin B Bridges, Fadi S Braiteh, Alexander N Starodub, Fa-Chyi Lee, Thomas E Gribbin, Donald A Richards, Marie Lee, Ronald L Korn, Neeta Pandit-Taskar, Stanley J Goldsmith, Charles M Intenzo, Arif Sheikh, Timothy C Manzone, Heather Horne, Robert M Sharkey, William A Wegener, Eileen M O'Reilly, David M Goldenberg, Daniel D Von Hoff
Abstract
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 (90)Y-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, (90)Y-clivatuzumab tetraxetan, weekly 6.5 mCi/m(2)doses×3, plus gemcitabine, weekly 200 mg/m(2) doses×4 starting 1 week earlier) or Arm B (N=29, (90)Y-clivatuzumab tetraxetan alone, weekly 6.5 mCi/m(2)doses×3), 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 3.4 months with multiple cycles (HR 0.32, P=0.004), including three patients in Arm A surviving >1 year.
Conclusions: Clinical studies of (90)Y-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.
Trial registration: ClinicalTrials.gov NCT01510561.
Keywords: Antibody; Clivatuzumab tetraxetan; Gemcitabine; Pancreatic cancer; Radioimmunotherapy; Yttrium-90.
Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Source: PubMed