Dendritic Cell–Based Immunotherapy Data in Resected Pancreatic Cancer Published in JCO

Treatment with the dendritic cell–based immunotherapy MesoPher led to a 2-year recurrence-free survival (RFS) rate of 64% and low-grade adverse effects (AEs) compared with the historical expected RFS rate of 40% in patients with resected pancreatic cancer following standard chemotherapy, according to updated findings from the phase 2 REACTIVE trial, which were published in the Journal of Clinical Oncology (JCO).^1,2

The 2-year overall survival (OS) rate was 83%, and translational immune profiling showed evidence of immune activation against the tumor.1 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.³

“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,” Professor Casper van Eijck, principal investigator of the trial and a pancreatic cancer surgeon at Erasmus MC in Rotterdam, Netherlands, stated in a news release.¹

Previously, MesoPher received orphan drug designation from the FDA and European Medicines Agency (EMA) for the treatment of patients with pancreatic cancer.¹ Prior findings from the trial announced in December 2022 indicated that the therapy produced a 2-year RFS rate of 60% among the 38 patients enrolled, meeting the primary end point of the study.²

The study was designed to evaluate the efficacy of dendritic cell–based immunotherapy in pancreatic cancer following earlier evidence highlighting a correlation between the treatment and induction of T-cell responses against pancreatic cancer antigens.³

The single-center, open-label, single-arm, combined phase 1/2 trial enrolled patients with pancreatic cancer following resection and completion of standard therapy without recurrent disease on cross-sectional imaging.³

Earlier findings from the first cohort of 10 patients were published in the European Journal of Cancer in 2022.4 Based on results showing that treatment was feasible, safe, and able to induce immune reactivity against malignant antigens, a second cohort of 28 patients was fully enrolled.²

Eligible patients received 3 biweekly injections of MesoPher and booster injections at 4 and 7 months.1,2 Specifically patients received autologous dendritic cells pulsed with an allogeneic mesothelioma tumor cell lysate, mixed with antigens that are also expressed in pancreatic ductal adenocarcinoma.³

The primary end point was the 2-year RFS rate. A clinically meaningful improvement could be claimed if the 2-year RFS rate was at least 60%.³

Thirty-eight patients were included in the analysis for the primary end point. Most patients were female (53%), and the median age was 62 years (interquartile range, 55-68). Twenty-eight patients (74%) received 5 dendritic cell vaccinations and completed the study protocol. Three patients (8%) received 4 vaccinations, and 7 patients (16%) received 3 vaccinations. Of the patients who received fewer than 5 vaccinations, 8 (80%) developed disease recurrence, and in 2 patients (20%), an insufficient number of dendritic cells were cultured for 5 vaccinations.³

After a median follow-up of 25.5 months (95% CI, 15.6-35.5), 26 patients (68%) had not developed disease recurrence. Among patients who developed recurrence (n = 12), 6 (50%) had local recurrence, 4 (33%) had distant recurrence, and 2 (17%) had local and distant recurrence. After disease recurrence, 9 patients (75%) started palliative chemotherapy. In patients with recurrence, 6 (50%) had died, and the median OS from the date of recurrence was 10.8 months (95% CI, 7.2-14.3).³

Regarding safety, 37 patients (97%) experienced grade 1 AEs, 7 patients (18%) experienced grade 2 AEs, and 1 patient (3%) experienced grade 3 dyspnea, which was determined to be possibly related to study treatment.³

“We have created a promising cell therapy bridgehead. MesoPher is derisked as to safety and manufacturing. This trial shows that MesoPher induces a clinically meaningful immune response, causing an increase in patient survival. The EMA has granted MesoPher orphan designation for pancreatic cancer, based on potential significant benefit. We are very happy to announce today that the FDA has granted MesoPher orphan designation for pancreatic cancer as well,” Ilona Enninga, chief operating officer of Amphera, added.¹

“The potential of MesoPher cell therapy is increasingly recognized in the scientific and regulatory community. The JCO publication will certainly help us to realize the necessary funding and partners for our next step: a randomized trial in resected pancreatic cancer,” Rob Meijer, chief executive officer of Amphera, said.¹

References

1. MesoPher cell therapy increases 2-year RFS rate in resected pancreatic cancer by 50%; publication of phase II results in Journal of Clinical Oncology and orphan designation granted by FDA & EMA. News release. Amphera. September 25, 2024. Accessed September 27, 2024. https://www.amphera.nl/mesopher-cell-therapy-increases-2-year-rfs-rate-in-resected-pancreatic-cancer-by-50-amphera-announces-publication-of-phase-ii-results-in-journal-of-clinical-oncology-and-orphan-designation-granted-by/
2. Amphera announces clinical updates of MesoPher cell therapy. News release. Amphera. December 12, 2022. Accessed September 27, 2024. https://www.amphera.nl/amphera-announces-clinical-updates-of-mesopher-cell-therapy/
3. Van’t Land FR, Willemsen M, Bezemer K, et al. Dendritic cell–based immunotherapy in patients with resected pancreatic cancer. J Clin Oncol. 2024;42(26):3083-3093. doi:10.1200/JCO.23.02585
4. Lau SP, Klaase L, Vink M, et al. Autologous dendritic cells pulsed with allogeneic tumour cell lysate induce tumour-reactive T-cell responses in patients with pancreatic cancer: a phase I study. Eur J Cancer. 2022;169:20-31. doi:10.1016/j.ejca.2022.03.015