A Clinical Study to Assess Safety and Efficacy of a Tumor Vaccine in Patients With Advanced Renal Cell Carcinoma (ASET)

Study Overview
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Brief Summary
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This is a Phase 1/2, proof-of-principle clinical study to assess safety and efficacy of a intradermally administered tumor vaccine (MGN1601). The study will be conducted in patients with advanced renal cell carcinoma.

Detailed Description
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Twenty four patients with advanced RCC will be included in this open, single-arm study. The treatment will last 12 weeks. The investigational product (MGN1601) will be administered intradermally for a total of 8 applications, whereas the first 3 applications will be administered weekly, and the following 5 applications will be administered bi-weekly. Patients who will develop disease control (CR, PR, or SD) by week 12 will be proposed to participate in the extension phase of the study. The extension phase will be continued until disease progression in each patient, however, maximally up to week 120 (total treatment duration 2.5 years). During this time period the investigational product will be administered 5 times by weeks 24, 36, 48, 72, and 120.

Official Title
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A Phase 1/2, Proof-of-Principle, Multi-Center, Open-Label, Single-Arm, Non-randomized Clinical Study to Assess Safety and Efficacy of a Tumor Vaccine Consisting of Genetically Modified Allogeneic (Human) Tumor Cells for the Expression of IL-7, GM-CSF, CD80 and CD154, in Fixed Combination With a DNA-based Double Stem Loop Immunomodulator in Patients With Advanced Renal Cell Carcinoma (ASET Study)

Conditions
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Stage IV Renal Cell Cancer

Intervention / Treatment
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* Biological: MGN1601


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects older than 18 years of age Histologically confirmed renal cell carcinoma Radiologically confirmed advanced disease defined as unresectable locally reccurrent or metastatic disease (AJCC Stage IV) Previous nephrectomy No standard therapy is available for the patient At least 4 weeks after previous radiotherapy prior to study treatment At least 1 week after previous systemic therapy prior to study treatment At least one lesion measurable by modified RECIST criteria ECOG performance status 0-1 Adequate organ function including hematopoietic organs MSKCC prognostic ctiteria < 3 predictors of short survival Negative urine pregnancy test in women with childbearing potential Women of childbearing potential and all male participants are willing to use acceptable methods of contraception (birth control pills, barriers) Expected adequacy of follow-up Signed informed consent form (ICF). Exclusion Criteria: Clinically significant concomitant diseases or conditions unrelated to the underlying malignancy or therapy, which in opinion of the investigator would lead to an unacceptable risk for the subject to participate in the study Known hypersensitivity to any component of the study drug Prior or current other malignancy, except adequately treated superficial bladder cancer, basal or squamous cell carcinoma of the skin or other cancer for which the subject has been disease free for more than 3 years Active brain metastases except adequately treated brain metastases with no progression for at least 3 months Active or uncontrolled infections Transfusion-dependent anemia History of autoimmune disease or immune deficiency Concurrent chronic systemic immune therapy, corticosteroids or other immunosuppressant medication Concurrent radiotherapy within the last 4 weeks prior to study treatment and/or during the course of the study Concurrent immunotherapy or targeted therapy within the last 1 week prior to study treatment and/or during the course of the study HIV seropositivity or active hepatitis B or C infection Planned major surgery during the study Participation in other clinical studies during this clinical study Vaccination within 3 months prior to the first treatment day Any medical, mental, psychological or psychiatric condition which in opinion of the investigator would not permit the subject to complete the study or understand the patient information Pregnancy and/or nursing Presence of drug and/or alcohol abuse Commitment to an institution by virtue of an order issued either by judicial or administrative authorities.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study medication<br> | Biological: MGN1601<br>* Genetically modified allogeneic (human) tumor cells for the expression of IL-7, GM-CSF, CD80 and CD154, in fixed combination with a DNA-based double stem loop immunomodulator (dSLIM)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of safety profile of MGN1601 |  | Treatment phase (12 weeks), extension phase (120 weeks, if applicable), plus 5 years follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of potential autoimmune effects of MGN1601 |  | Treatment phase (12 weeks), extension phase (120 weeks, if applicable) plus 5 years follow-up (if applicable) | 
| Assessment of the presence of MIDGE vectors |  | Treatment phase (12 weeks) | 
| Assessment of the immune response to MGN1601 |  | Treatment phase (12 weeks), extension phase (120 weeks, if applicable) | 
| Evaluation of clinical and radiological response to MGN1601 |  | Treatment phase (12 weeks), extension phase (120 weeks, if applicable) plus 5 years follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Renal Cell Carcinoma, Tumor Vaccine, Cell-based Therapy