Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer
A newer report of this study has been published: RNA neoantigen vaccines prime long-lived CD8(+) T cells in pancreatic cancer (2025)
- Study type
- Clinical trial
- Study name
- Autogene cevumeran PDAC
- Phase
- Phase 1
- Design
- Single-arm, single-centre trial (Memorial Sloan Kettering), adjuvant treatment after surgery
- Sample size
- 34 patients enrolled; 19 received atezolizumab and 16 received the vaccine
- Source
- Nature · 2023
- Trial registration
- NCT04161755
In plain words
Pancreatic cancer often comes back, even after successful surgery. In this small study, each patient's removed tumour was used to make a personal mRNA vaccine, and it was possible to make and give it in time. In half of the patients, the vaccine produced strong immune cells against the tumour, and in this group the cancer came back much later during follow-up. This is an early study with no comparison group, and the treatment is still experimental; a larger trial is under way.
Key results
Treatment arms and regimens
Atezolizumab a single dose of 1200 mg IV at week 6 after surgery.
Autogene cevumeran (BNT122/RO7198457) 9 doses of 25 micrograms IV: 7 weekly priming doses from week 9, an eighth dose at week 17 and a ninth booster dose at week 46 (up to 20 neoantigens per patient).
mFOLFIRINOX (folinic acid, fluorouracil, irinotecan and oxaliplatin) 12 cycles from week 21; the doses of the mFOLFIRINOX drugs are not given in the paper or on ClinicalTrials.gov.
Autogene cevumeran is an investigational drug and is not approved.
Source of the regimen details: Full text of the paper in PMC (PMC10171177), Methods section; ClinicalTrials.gov NCT04161755
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 resectable pancreatic ductal adenocarcinoma (PDAC) who underwent tumour resection. From December 2019 to August 2021, 34 patients were enrolled, of whom 28 underwent surgery; 19 received atezolizumab, of whom 16 received the autogene cevumeran vaccine, and 15 then received mFOLFIRINOX.
Endpoints
Primary endpoint: safety.
Secondary endpoints: 18-month recurrence-free survival and 18-month overall survival; also vaccine-induced neoantigen-specific T cells and oncological feasibility (treatment timing).
Safety and side effects
None of the 19 patients who received atezolizumab had a grade 3 or higher adverse event. One of 16 patients (6%) who received autogene cevumeran had a grade 3 event (fever and hypertension). All 16 patients had grade 1 to 2 adverse events. The vaccine was given a median of 3 days from the target schedule.
Clinical significance and place in guidelines
This study showed that real-time manufacture of an individualised neoantigen mRNA vaccine within routine pancreatic cancer care is feasible and immunogenic, even in a tumour with a low mutational burden. These findings formed the basis of the randomised phase 2 trial IMCODE003 (NCT05968326), which compares autogene cevumeran with atezolizumab and mFOLFIRINOX versus mFOLFIRINOX alone. Autogene cevumeran has no FDA or EMA approval and is an investigational treatment.
Limitations
This is a single-arm, single-centre phase 1 trial with very few patients (16 vaccinated) and no randomised control group. The comparison of responders and non-responders is correlative and does not prove causation. All participants were white, and adjuvant chemotherapy started later than usual (week 21).
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.