Abstract 43P
Background
Immune checkpoint blockers (ICB) have revolutionized the therapeutic landscape in non-small cell lung cancer (NSCLC). However, most patients do not show durable responses. This calls for additional strategies to re-ignite cellular immunity against the tumor. We have developed MIDRIX, an autologous mRNA-dendritic cell-based therapy capable of eliciting robust tumor-antigen specific cytotoxic T cell responses and strong type 1 T-helper polarization. MIDRIX4-LUNG specifically targets 4 highly cancer-restricted antigens that combined cover more than 90% of all NSCLC-cases. The antigens are encoded as full-length mRNA sequences optimized to induce CD8 and CD4 T cell responses in an HLA-independent matter.
Methods
This is a phase Ia first-in-human, intra-patient dose escalation trial. Eligible patients were adults with metastatic NSCLC not amenable for standard-of-care anti-tumoral therapy at the time of enrollment. After leukapheresis, patients received up to 5 intravenous infusions of DCs with a maximum dose of 100 × 10E6 DCs. The primary endpoint was safety. Secondary endpoints were feasibility, immune responses, tumor response and progression-free survival.
Results
Seven patients were included between November 2019 and September 2020. One subject died due to rapid disease progression during screening. Six patients underwent leukapheresis which was well tolerated (grade 2 hypocalcaemia in 2/6 patients). At least 3 doses could be manufactured in 5/6 patients. The most common adverse events were dizziness (N=3), fatigue (N=3), nausea (N=2) and flu-like symptoms (N=2). The best objective response was stable disease in 3 subjects. Median progression free survival was 2,4 months (95% CI 1,1–6,2). Three patients developed an immune response against one or more target antigens. Both CD8 and CD4 T cell responses were observed.
Conclusions
MIDRIX4-LUNG is the first tetravalent mRNA-modified DC therapy for NSCLC. Producing and administering this cellular therapy is feasible in this heavily pre-treated patient population. No dose limiting toxicity was observed. Clinical and immunological outcomes are encouraging. A follow-up trial combining MIDRIX4-LUNG with ICB is now in development.
Clinical trial identification
NCT04082182.
Legal entity responsible for the study
The authors.
Funding
Kom op tegen Kanker.
Disclosure
All authors have declared no conflicts of interest.