Background: Immunotherapy has limited applicability in the treatment for CRPC patients (pts). An advantageous effect of immune stimulation in CRPC pts was shown by sipuleucel-T, a dendritic cell (DC)-based vaccine. Vaccination (Vac) strategies using myeloid and plasmacytoid DC (mDC and pDC) may improve immunological and clinical outcome of CRPC pts.
Methods: In this randomised phase II trial, 21 HLA-A*02.01 positive chemo-naive CRPC pts received maximally 3 cycles of 3 Vac consisting of mDC, pDC or combined mDC + pDC, loaded with tumour-associated antigens (MUC1, NY-ESO-1, and MAGE-C2). Radiological responses were assessed on 68Ga-PSMA PET-CT scan for RECIST 1.1, iron oxide-enhanced MRI scan of lymph nodes and MRI bones. Primary endpoint is the immunological response after DC Vac. Secondary endpoints are safety, feasibility, PSA responses, radiological PFS and OS.
Results: All vaccine types were well tolerated, 14 out of 21 pts had grade 1-2 toxicity. There was no grade 3-4 toxicity observed. After 6 months, no radiological disease progression was observed in 62% (13 out of 21 pts). At 12 months follow-up, 45% of patients (5 out of 11) showed stable disease. Mean radiological PFS was 6.1 months (95% CI: 3.7-8.6). No difference between the groups was observed. One patient had a partial radiological response and a significant drop in PSA level from 120 ng/ml to 3.4 ng/ml. Radiological stable pts showed preVac a PSA doubling time of 6.9 months (95% CI: 3.8-10.1), at 6 months after randomisation this was 13.1 months (95% CI: 4.9-21.2). Over a median follow-up period of 12.0 months, median OS was not reached. Primary immunological outcome will be presented.
Conclusions: Myeloid and plasmacytoid DC Vac is feasible and safe in early CRPC pts, with preliminary results hinting at possible clinical efficacy. This warrants further study. Clinical trial information: NCT02692976