Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

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Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Vaccines

Immunomodulating Agents

Immunologic Factors

Intra-patient dose escalation of intravenous MIDRIXNEO-LUNG autologous DC vaccine

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

Dendritic cell immunotherapy

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)

Antigen-specific 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)

Control DTH

Karim Y Vermaelen, MD, PhD

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.

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.

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

Toxicity measures as defined by common toxicity criteria v5.0. The maximal tolerated and/or feasible dose will be defined from the intra-patient dose excalation scheme

Success rate (%) of producing sufficient dendritic cells for vaccination

Vaccine-induced immunological responses as measured by in vitro immunomonitoring assays

Vaccine-induced immunological responses as measured by in vivo immunomonitoring test (delayed-type hypersensitivity skin reaction)

Relapse-free survival based on clinical and/or radiological event

University Ghent

Kom Op Tegen Kanker

University Hospital, Ghent

Intra-patient dose escalation of intravenous MIDRIX4-LUNG autologous DC vaccine

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

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)

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.

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.

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

Safety and tolerability of preparing and administrating an autologous dendritic cell-based vaccine in advanced non-small cell lung cancer patients.

The maximal tolerated dose will be defined from the intra-patient dose excalation scheme

Feasibility of producing sufficient dendritic cell for vaccination in advanced NSCLC

Biological activity of the vaccine (elicitation of immune responses against vaccine antigens) using a series of in vitro assays probing for antigen-specific T-cell reactivity

Vaccine-induced antigen-specific immunological responses as measured by delayed-type hypersensitivity skin reaction

Relapse-free survival (months), based on objective tumor measurements per RECIST 1.1

Median progression-free survival (months), based on objective tumor measurements per RECIST 1.1

Progression-free survival at landmark timepoints (%), based on objective tumor measurements per RECIST 1.1

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
MIDRIXNEO-LUNG Dendritic Cell Vaccine in Patients With Non-small Cell Lung Cancer	NCT04078269	Non-small Cell ...	Dendritic cell ... Antigen-specifi... Control DTH	18 Years -	University Hospital, Ghent
MIDRIX4-LUNG Dendritic Cell Vaccine in Patients With Metastatic Non-small Cell Lung Cancer	NCT04082182	Non-small Cell ...	Dendritic cell ... Antigen-specifi... Control DTH	18 Years -	University Hospital, Ghent

Spots Global Cancer Trial Database for control dth

Every month we try and update this database with for control dth cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for control dth

Every month we try and update this database with for control dth cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for control dth cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.