NCT04078269

MIDRIXNEO-LUNG Dendritic Cell Vaccine in Patients With Non-small Cell Lung Cancer

Phase I Study of MIDRIXNEO-LUNG, an Autologous Neoantigen-targeted Dendritic Cell Immunotherapy in Patients With Non-small Cell Lung Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: University Hospital, Ghent · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

MIDRIXNEO-LUNG is a novel autologous dendritic cell vaccine for non-small cell lung cancer patients, targeting neoantigens predicted from the patient-individual tumor's mutanome. This first-in-human study aims to primarily establish maximal tolerated dose of MIDRIXNEO-LUNG administered i.v.

Detailed description

Immunotherapy, in the shape of immune checkpoint inhibitors, is now being investigated as an adjuvant therapy in resected NSCLC, with issues unsolved with respect to the optimal duration of treatment, in addition to the unpredictable nature of side-effects with this class of compounds. Also, it is known from advanced disease stages that only a minority of patients respond to checkpoint inhibitors. An alternative, highly targeted immunotherapeutic approach with an excellent safety track record consists of vaccination. Cancer vaccines aims to prime and/or expand tumor antigen-targeting T-cells and induce immunological memory against later disease relapse. Whereas immune checkpoint blockade boosts inactivated responses of effector T cells, vaccination can potentially activate naive T cells with tumor specificity and in this way broaden the tumor-specific immune responses. However, simple protein-based cancer vaccines have failed in lung cancer so-far, suggesting that the optimal vaccination modality for NSCLC still needs to be established. Dendritic cells (DCs) are specialized antigen presenting leukocytes that are now recognized as the central controllers of the immune response. The DCs unique capacity to induce robust, highly antigen-specific cytotoxic T-cell responses has led to the use of in vitro-generated autologous DCs as cancer vaccines. The investigators have developed a novel DC vaccine design that combines robust immunogenicity together with the targeting of patient-tumor specific mutations, also known as neoantigens. The DC vaccine is produced in 2 stages: (1) First, DNA and RNA is isolated from the surgical tumor specimen, sequenced and the sequence is compared to blood cell DNA. In this way, the tumor-specific mutations are identified and the most immunogenic mutated sequences are synthetized. This process takes 3-4 months starting from surgical resection of the tumor. (2) Next, patients undergo a leukapheresis for the harvest of monocytes which are differentiated in vitro into activated DCs. The DCs are finally loaded with the neoantigen-encoding sequences, producing the IMP, MIDRIXNEO.

Conditions

• Non-small Cell Lung Cancer

Interventions

Type	Name	Description
BIOLOGICAL	Dendritic cell immunotherapy	Intravenous infusions of MIDRIXNEO-LUNG DCs every 2 weeks, using an intra-patient dose escalation scheme progressing along the following range: 10 x10E6 DCs (minimal dose), 20 x 10E6 DCs, 40 x 10E6 DCs, 80 x 10E6 DCs, 100 x 10E6 DCs (maximal dose), until exhaustion of the batch or occurrence of grade ≥3 toxicity event
BIOLOGICAL	Antigen-specific DTH	Intradermal injection of 1 x 10E6 MIDRIXNEO-LUNG DCs at baseline and after completion of all i.v. DC vaccination rounds. This is used for assessment of induction of antigen-specific immune responses as part of in vivo immunomonitoring (delayed-type hypersensitivity cutaneous reaction as test read-out)
BIOLOGICAL	Control DTH	Intradermal injection of 1 x 10E6 MIDRIX-CTRL DCs at baseline and after completion of all i.v. DC vaccination rounds. This is used for assessment of background (i.e. non-antigen-specific) reactivity (delayed-type hypersensitivity cutaneous reaction as test read-out)

Timeline

• Start date: 2019-08-26
• Primary completion: 2024-02-01
• Completion: 2025-03-03
• First posted: 2019-09-06
• Last updated: 2025-04-29

Locations

1 site across 1 country: Belgium