Updated findings from the phase 2 REACTIVE trial, published in the Journal of Clinical Oncology, reveal that treatment with the dendritic cell–based immunotherapy MesoPher led to a 2-year recurrence-free survival (RFS) rate of 64% in patients with resected pancreatic cancer following standard chemotherapy. This is compared to the historical expected RFS rate of 40%.
The single-center, open-label trial enrolled patients with pancreatic cancer following resection and completion of standard therapy without recurrent disease. Patients received three biweekly injections of MesoPher, followed by booster injections at 4 and 7 months. MesoPher consists of autologous dendritic cells pulsed with an allogeneic mesothelioma tumor cell lysate, mixed with antigens also expressed in pancreatic ductal adenocarcinoma.
REACTIVE Trial Results
The 2-year overall survival (OS) rate was 83%. Translational immune profiling showed evidence of immune activation against the tumor. Specifically, vaccination resulted in an abundance of circulating activated CD4-positive T cells and led to the detection of treatment-induced immune responses in vitro. T-cell receptor–sequencing analyses of a resected solitary lung metastasis also pointed to an influx of vaccine-specific T cells.
After a median follow-up of 25.5 months (95% CI, 15.6-35.5), 26 of 38 patients (68%) had not developed disease recurrence. Among the 12 patients who developed recurrence, 6 (50%) had local recurrence, 4 (33%) had distant recurrence, and 2 (17%) had both local and distant recurrence. Following recurrence, 9 patients (75%) started palliative chemotherapy. The median OS from the date of recurrence was 10.8 months (95% CI, 7.2-14.3).
Safety and Tolerability
Regarding safety, 37 patients (97%) experienced grade 1 adverse events (AEs), 7 patients (18%) experienced grade 2 AEs, and 1 patient (3%) experienced grade 3 dyspnea, which was possibly related to the study treatment.
Expert Commentary
Professor Casper van Eijck, principal investigator of the trial and a pancreatic cancer surgeon at Erasmus MC in Rotterdam, Netherlands, stated, “These results are promising as recurrence rates are high and long-term survival is rare in this patient group. We are now preparing a randomized phase 2/3 trial to replicate this efficacy signal. I am happy to announce that the Dutch Pancreatic Cancer Group, one of the world’s leading research groups in this field, has committed to participate in this trial.”
Regulatory Designations and Future Directions
MesoPher has received orphan drug designation from the FDA and European Medicines Agency (EMA) for the treatment of patients with pancreatic cancer. Rob Meijer, chief executive officer of Amphera, noted, “The potential of MesoPher cell therapy is increasingly recognized in the scientific and regulatory community...[which] will certainly help us to realize the necessary funding and partners for our next step: a randomized trial in resected pancreatic cancer.”
