Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Immunomodulating Agents

Antimetabolites

1000 mg/m2 intravenoulsy once a week according to protocol schedule

The cells will be administered by intratumoral injection on 2 different days(at least 21 days apart)

Dendritic Cell Immunotherapy

Edgar G Engleman

George Albert Fisher M.D. Ph.D.

To determine the safety, feasibility and appropriate dendritic cell dose to vaccinate patients with pancreas cancer

Phase I/II Intratumoral DC Immunotherapy With Gemcitabine & XRT in Unresectable Pancreatic Cancer

A Phase I/II Trial of Intratumoral Dendritic Cell Immunotherapy in Combination With Gemcitabine and Stereotactic Radiosurgery in Unresectable Pancreatic Cancer

George Albert Fisher

Associate Professor of Medicine

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Vaccines

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

Prof Dr Karim Vermaelen

Nervous System Diseases

Glioblastoma

Glioma

Brain Neoplasms

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroepithelioma

Two intradermal (i.d.) injections of DCVax-L(treatment cohort) or autologous PBMC (placebo cohort) per treatment. Treatments will be given at days 0, 10, 20, and at weeks 8, 16, 32, 48, 72, 96 and 120.

Linda Liau, M.D.

Marnix L. Bosch, MBA, PhD

The primary purpose of the study is to determine the efficacy of an investigational therapy called DCVax(R)-L in patients with newly diagnosed GBM for whom surgery is indicated. Patients must enter screening at a participating site prior to surgical resection of the tumor. Patients will receive the standard of care, including radiation and Temodar therapy and two out of three will additionally receive DCVax-L, with the remaining one third receiving a placebo. All patients will have the option to receive DCVax-L in a crossover arm upon documented disease progression. (note: DCVax-L when used for patients with brain cancer is sometimes also referred to as DCVax-Brain)

This Phase III trial is designed to evaluate the impact on survival time, as well as safety, in patients following treatment with DCVax(R)-L, an immunotherapy treatment for GBM. The experimental therapy uses a patient's own tumor lysate and white blood cells from which precursors of the dendritic cells are isolated. The dendritic cell is the starter engine of the immune system. The white cells are then made into dendritic cells and they are educated to "teach" the immune system how to recognize brain cancer cells. Eligible patients will receive a series of injections of DCVax-L, to activate and then boost the immune response to the tumor cells.

The primary study endpoint is OS (overall survival) compared to external controls in newly diagnosed glioblastoma, and the first secondary endpoint is OS compared to external controls in recurrent glioblastoma.

Side effects reported from early trials are mostly mild, and may include skin reactions of redness, pain \& swelling at the injection site.

Study of a Drug [DCVax®-L] to Treat Newly Diagnosed GBM Brain Cancer

A Phase III Clinical Trial Evaluating DCVax®-L, Autologous Dendritic Cells Pulsed With Tumor Lysate Antigen For The Treatment Of Glioblastoma Multiforme (GBM)

Northwest Biotherapeutics

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Hormones

The purpose of this clinical research study is to assess the safety and efficacy of an investigational therapy called DCVax(TM)-Prostate.

Patients with hormone refractory prostate cancer are eligible if they have a rising PSA or three or fewer metastatic lesions. The experimental therapy uses a patient's own white blood cells and "teaches" the cells to recognize a "flag" on prostate cancer cells. This may help the immune system destroy prostate cancer cells. Side effects reported from the Phase I/II trial include skin reactions of redness, pain \& swelling at the injection site, and short-lived headache, fever \& fatigue. Full details are available in the informed consent.

Study of a Drug [DCVax (tm)-Prostate] to Treat Prostate Cancer When Hormone Therapy is no Longer Effective.

A Randomized, Double-blind, Placebo-controlled Phase III Clinical Trial Evaluating DCVax(tm)-Prostate, Autologous Dendritic Cells Loaded With Recombinant PSMA for the Treatment of Metastatic Hormone Refractory Prostate Cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I/II Intratumoral DC Immunotherapy With Gemcitabine & XRT in Unresectable Pancreatic Cancer	NCT00547144	Pancreatic Canc...	Gemcitabine Dendritic Cell ...	18 Years -	Stanford University
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
Study of a Drug [DCVax®-L] to Treat Newly Diagnosed GBM Brain Cancer	NCT00045968	Glioblastoma Mu... Glioblastoma GBM Grade IV Astroc... Glioma Brain Cancer Brain Tumor	Dendritic cell ...	18 Years - 70 Years	Northwest Biotherapeutics
Study of a Drug [DCVax (tm)-Prostate] to Treat Prostate Cancer When Hormone Therapy is no Longer Effective.	NCT00043212	Prostate Cancer	Dendritic cell ...	18 Years -	Northwest Biotherapeutics
Phase I/II Intratumoral DC Immunotherapy With Gemcitabine & XRT in Unresectable Pancreatic Cancer	NCT00547144	Pancreatic Canc...	Gemcitabine Dendritic Cell ...	18 Years -	Stanford University

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