A neoantigen vaccine generates antitumour immunity in renal cell carcinoma
- Study type
- Clinical trial
- Study name
- NeoVax RCC (NCT02950766)
- Phase
- Phase 1
- Design
- Phase 1, two-arm, non-randomised trial (vaccine with or without local subcutaneous ipilimumab)
- Sample size
- 9 patients (5 vaccine + ipilimumab, 4 vaccine alone)
- Source
- Nature · 2025
- Trial registration
- NCT02950766
In plain words
Some patients are at high risk of their kidney cancer coming back after surgery. In this small study, a personal peptide vaccine was made for each patient based on the mutations in their own tumour. The vaccine triggered an immune response in all 9 patients, and over about 3 and a half years of follow-up the disease did not come back in any of them. Side effects were mostly mild (redness at the injection site and cold-like symptoms). However, the number of patients is very small and this vaccine is still experimental.
Key results
Treatment arms and regimens
Personalised neoantigen peptide vaccine (NeoVax): 4 pools, each of up to 5 synthetic long peptides (300 µg of each peptide) mixed with 0.5 mg poly-ICLC per pool; half the dose given subcutaneously and half intradermally. Schedule: days 1, 4, 8, 15 and 22 (priming), then weeks 12 and 20 (boost).
Ipilimumab 2.5 mg subcutaneously at each vaccine site, within 1 cm of the injection site.
Note: this vaccine is a peptide vaccine (not mRNA) and is investigational and unapproved.
The same peptide vaccine and schedule (days 1, 4, 8, 15 and 22 and weeks 12 and 20), without ipilimumab.
Source of the regimen details: Full text of the paper in PMC (PMC11903305), Methods section; ClinicalTrials.gov NCT02950766
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 high-risk stage III or IV clear cell renal cell carcinoma (clear cell RCC) whose tumour had been completely removed by surgery. 7 patients (78%) had stage III and 2 (22%) stage IV disease; enrolment between March 2019 and September 2021.
Endpoints
Primary objectives: safety and tolerability of the vaccine given with local (subcutaneous) ipilimumab, and determination of the maximum tolerated dose of local ipilimumab.
Secondary objectives: induction of neoantigen-specific cellular immune responses after vaccination, and the proportion of patients alive and relapse-free 2 years after surgery.
Safety and side effects
No dose-limiting toxicities or grade 3 or higher adverse events were observed. The most common treatment-related adverse events were injection-site reactions (grade 1: 78%; grade 2: 22%) and influenza-like symptoms (grade 1: 67%; grade 2: 22%). All 9 patients had an inflammatory skin reaction at the injection site.
Clinical significance and place in guidelines
This study showed that a personalised neoantigen vaccine, even in a cancer with a moderate mutational burden such as kidney cancer, can target driver mutations and generate antitumour immunity. This is a peptide vaccine (not mRNA), and larger randomised trials are needed to prove efficacy. It has no FDA or EMA approval, and standard adjuvant therapy for high-risk RCC remains pembrolizumab.
Limitations
Phase 1 trial with only 9 patients and no control group; the absence of relapse cannot be compared directly with phase 3 adjuvant trials. The arms were not randomised, and the effect of adding ipilimumab cannot be assessed precisely. Making an individualised vaccine is time-consuming and costly. A third arm (ipilimumab 5 mg) is not reported in this analysis.
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.