RNA neoantigen vaccines prime long-lived CD8(+) T cells in pancreatic cancer
- Study type
- Clinical trial
- Study name
- Autogene cevumeran PDAC
- Phase
- Phase 1
- Design
- Long-term follow-up of a single-arm phase 1 trial with immunological analyses (T-cell clone tracking)
- Sample size
- 16 vaccinated patients (8 responders, 8 non-responders); 19 patients in the safety-evaluable group
- Source
- Nature · 2025
- Trial registration
- NCT04161755
In plain words
This report looked again at the patients from the same small personal pancreatic cancer vaccine study about 3 years later. In patients in whom the vaccine had produced an immune response, the anti-tumour immune cells stayed in the body for years, and in most of them the cancer had not come back. These results are encouraging, but the study is very small with no comparison group, and this vaccine is still experimental.
Key results
Treatment arms and regimens
The same regimen as the phase 1 trial: atezolizumab a single dose of 1200 mg IV at week 6 after surgery; autogene cevumeran 9 doses of 25 micrograms IV (7 weekly doses from week 9, an eighth dose at week 17 and a booster dose at week 46); then 12 cycles of mFOLFIRINOX from week 21.
Autogene cevumeran is an investigational drug and is not approved.
Source of the regimen details: Full text of the initial paper in PMC (Rojas et al., Nature 2023; PMC10171177), Methods section
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with resected pancreatic ductal adenocarcinoma (PDAC) in the phase 1 trial of autogene cevumeran (NCT04161755). Median follow-up 3.2 years (range 2.3 to 4.0 years); data cut-off 1 December 2023.
Endpoints
Recurrence-free survival and overall survival at long-term follow-up by immune response to the vaccine; lifespan, frequency, phenotype and function of vaccine-induced CD8+ T-cell clones.
Safety and side effects
This paper focuses on immunological and clinical follow-up; safety data are in the initial report (Rojas et al., Nature 2023): one of 16 vaccinated patients had a grade 3 adverse event (fever and hypertension).
Clinical significance and place in guidelines
This study provides important biological evidence that mRNA neoantigen vaccines can generate long-lived T cells, and the association between immune response and delayed recurrence held up with longer follow-up. Clinical efficacy is being evaluated in the randomised phase 2 trial IMCODE003 (NCT05968326). Autogene cevumeran has no FDA or EMA approval.
Limitations
The number of patients is very small (16 vaccinated) and there is no randomised control group; the comparison of responders and non-responders is correlative and may be influenced by other factors. Estimates of clone lifespan are based on mathematical modelling.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.