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 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 6.5 mCi/m² doses × 3, plus gemcitabine, weekly 200 mg/m² doses × 4 starting 1 week earlier) or Arm B (N = 29, ⁹⁰Y-clivatuzumab tetraxetan alone, weekly 6.5 mCi/m² 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 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.