NCT04082182

MIDRIX4-LUNG Dendritic Cell Vaccine in Patients With Metastatic Non-small Cell Lung Cancer

Phase Ia Study of MIDRIX4-LUNG, a Tetravalent Autologous Dendritic Cell Vaccine, in Patients With Metastatic Non-small Cell Lung Cancer

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 7 (actual)
• Sponsor: University Hospital, Ghent · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

MIDRIX4-LUNG is a novel tetravalent autologous dendritic cell vaccine in metastatic non-small cell lung cancer patients. This first-in-human study aims to primarily establish maximal tolerated dose of MIDRIX4-LUNG administered i.v.

Detailed description

Immunotherapy, in the shape of immune checkpoint inhibitors, is transforming the therapeutic landscape of non-small cell lung cancer. Checkpoint inhibitors can deliver durable tumor regressions, however only a minority of patients derive this kind of benefit, even with recent combinatorial approaches. It is clear from these clinical results that the full anti-tumoral power of the immune system is not being leveraged yet. Vaccination 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 that are the target of immune checkpoint inhibition. However, 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 method for the rapid production of DCs with all the required features for the induction of anti-tumor immunity. The cells are particularly potent in inducing type 1-polarized T-helper cell and antigen-specific cytolytic T-cell responses. The DCs are loaded with a proprietary selection of 4 antigens that cover \>90% of all NSCLC patients. With the objective of ultimately combining this DC vaccine with immune checkpoint inhibition, the investigators will first establish feasibility and maximal tolerated dose of DC vaccination as monotherapy using an intra-patient dose escalation scheme.

Conditions

• Non-small Cell Lung Cancer Metastatic

Interventions

Type	Name	Description
BIOLOGICAL	Dendritic cell immunotherapy	Intravenous infusions of MIDRIX4-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 MIDRIX4-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: 2021-06-07
• Completion: 2021-12-31
• First posted: 2019-09-09
• Last updated: 2021-03-30

Locations

1 site across 1 country: Belgium