90Y-clivatuzumab tetraxetan with or without low-dose gemcitabine: A phase Ib study in patients with metastatic pancreatic cancer after two or more prior therapies

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 Y-90-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, Y-90-clivatuzumab tetraxetan, weekly 6.5 mCi/m(2) doses x 3, plus gemcitabine, weekly 200 mg/m(2) doses x 4 starting 1 week earlier) or Arm B (N = 29, Y-90-clivatuzumab tetraxetan alone, weekly 6.5 mCi/m(2) doses x 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 Y-90-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. (C) 2015 The Authors. Published by Elsevier Ltd.