Abstract 2268
Background
Castrate-resistant prostate cancer (CRPC) is a deadly disease which warrants new therapies. Clinical evidence supports a beneficial effect of immune stimulation in CRPC patients shown by sipuleucel-T. Dendritic cells (DC) are the immune system’s professional antigen presenting cells. The use of new DC subpopulations could improve their outcome.
Methods
In this phase II trial, HLA-A*02.01 positive chemo-naive CRPC patients were randomly assigned (1:1:1) to myeloid DC (mDC), plasmacytoid DC (pDC) or combined mDC + pDC vaccinations. Patients had disease progression by rising PSA or increase in measurable disease by RECIST 1.1 and PCWG2. Patients received DC vaccination loaded with the tumor-associated antigens MUC1, NY-ESO-1, and MAGE-C2. Radiological responses were assessed on 68Ga-PSMA PET-CT scan (incl. RECIST 1.1), iron oxide-enhanced MRI scan of lymph nodes (nano-MRI) and MRI bones. Primary endpoint is the immunological response post-DC vaccination. Main secondary endpoints are safety and feasibility, radiological PFS and PSA response.
Results
We present the early clinical results of the first 12 patients. Patients were assigned to mDC vaccinations (n=5), pDC vaccinations (n=5) or combined mDC + pDC vaccinations (n=2). All vaccine types were tolerated well (grade 1-2 toxicity in 4/12 patients). Most importantly, 8 of 12 patients (67%) showed radiological stable disease after 6 months using PSMA PET-CT scanning confirmed by (nano-) MRI scans. In patients with at least 9 months follow-up (n=6), 5 still show stable disease. Radiological stable patients showed a trend to an increased PSA doubling time (PSAdt); prevaccination PSAdt was 8.7 months (95% CI: 4,0-13,3) vs. 19.9 months (95% CI: 10,4-29,3) at 6 months.
Clinical responses in the first twelve CRPC patients treated with blood-derived DC vaccinations.
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| AA: oral anti-androgen therapy (bicalutamide in nine patients and abiraterone plus dexamethason in one patient); DC: dendritic cells; GS: Gleason score; FLS: flu-like symptoms; LHRH: luteinizing hormone-releasing hormone; LN: lymph nodes; mo: months; PD: progressive disease; PSAdt: prostate-specific antigen doubling time; SD: stable disease; SO: subcapsular orchidectomy; UTI: urinary tract infection; vac: vaccinations. ^ vaccination with mDC (patients 1-5), pDC (patients 6-10) or combined mDC + pDC (patient 11 and 12). # only vaccine-related Common Terminology Criteria for Adverse Events grade 1-2 side effects were seen. The UTI was related to progressive LN metastases. $ radiological responses were assessed on advanced imaging with 68Ga-PSMA PET CT scans, nano-MRIs and MRI bones using RECIST 1.1 and PCWG2 criteria. * radiological and biochemical progression of disease was already present after 4 months, whereupon DC vaccinations were stopped. |
Conclusions
Innovative DC vaccination is feasible and safe in early CRPC patients. Clinical results of the first 12 vaccinated patients showed radiological stable disease in 67% of patients at 6 months.
Clinical trial identification
ClinicalTrials.gov Identifier: NCT02692976. First received: September 30, 2015