First-in-human Interleukin-15-transpresenting Wilms' Tumor Protein 1-targeting Autologous Dendritic Cell Vaccination in Cancer Patients

NCT05964361 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: CCRG19-001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to investigate a new type of dendritic cell vaccine in patients with refractory or advanced solid tumors of the esophagus, liver, pancreas and ovaries. The main questions it aims to answer are:

• is it feasible to produce and administer these dendritic cell vaccines?
• is treatment with these dendritic cell vaccines safe? Participants will first need to undergo a leukapheresis procedure to collect the cellular starting material for the dendritic cell vaccine production. The treatment consists of 6 vaccines, administered at biweekly intervals. Participants will be followed-up until 90 days after the last vaccine.

Conditions

Esophageal Cancer; Pancreas Cancer; Ovarian Cancer; Liver Cancer

Outcome Measures

Primary Outcomes (7)

• Feasibilty of leukapheresis

  Proportion of patients in the intention-to-treat population that had a successful leukapheresis.

  Upon completion of leukapheresis, on average 4 weeks after inclusion (baseline)

• Feasibility of IL15/IL15Ra/WT1 DC vaccine production

  Proportion of patients in the intention-to-treat population that had successful vaccine production (i.e. production of at least 6 IL-15-transpresenting WT1-targeting DC vaccines meeting all quality control measurements).

  Upon completion of vaccine production and quality testing (i.e. from leukapheresis until 4 weeks after), on average 8 weeks after inclusion (baseline)

• Feasibility of study treatment scheme

  Proportion of patients in the intention-to-treat population who complete the study treatment schedule of 6 IL-15-transpresenting WT1-targeting DC vaccines.

  Study treatment scheme (i.e. from administration of first to 6th vaccine (+- 10 weeks))

• Feasibility of DC vaccine administration (administration of 1st vaccine)

  Proportion of efficacy evaluable patients (i.e. having received at least 1 vaccine + no major protocol violation) in the intention-to-treat population.

  At administration of first vaccine

• Safety of IL15/IL15Ra/WT1 DC vaccine administration: Related (Severe) Adverse Events ((S)AEs)

  Proportion of patients of the safety population that experienced (S)AEs possibly, probably or definitely related to IL15/IL15Ra/WT1 DC vaccination

  over the entire study duration (i.e. from inclusion (baseline) to end of follow-up, which lasts until 90 days after the last DC vaccine), on average 7 months

• Safety of IL15/IL15Ra/WT1 DC vaccine administration: total (S)AEs (number)

  Number of (S)AEs in the safety population (i.e. having received at least 1 DC vaccine)

  over the entire study duration (i.e. from inclusion (baseline) to end of follow-up, which lasts until 90 days after the last DC vaccine), on average 7 months

• Safety of IL15/IL15Ra/WT1 DC vaccine administration: total (S)AEs (grade)

  Grade of (S)AEs in the safety population

  over the entire study duration (i.e. from inclusion (baseline) to end of follow-up, which lasts until 90 days after the last DC vaccine), on average 7 months

Secondary Outcomes (11)

• Indicators of clinical efficacy: Best Overall Response (BOR)

  over the entire study duration (i.e. from inclusion (baseline) to end of follow-up, which lasts until 90 days after the last DC vaccine), on average 7 months

• Indicators of clinical efficacy: Duration of Response (DOR)

  over the entire study duration (i.e. from inclusion (baseline) to end of follow-up, which lasts until 90 days after the last DC vaccine), on average 7 months

• Indicators of clinical efficacy: Objective Response Rate (ORR)

  over the entire study duration (i.e. from inclusion (baseline) to end of follow-up, which lasts until 90 days after the last DC vaccine), on average 7 months

• Indicators of clinical efficacy: Disease Control Rate (DCR)

  over the entire study duration (i.e. from inclusion (baseline) to end of follow-up, which lasts until 90 days after the last DC vaccine), on average 7 months

• Indicators of clinical efficacy: Progression-free Survival (PFS)

  over the entire study duration (i.e. from inclusion (baseline) to end of follow-up, which lasts until 90 days after the last DC vaccine), on average 7 months. PFS may be updated after study completion.

Interventions

IL15-transpresenting WT1-targeted Dendritic Cell Vaccine BIOLOGICAL

IL15/IL15Ra/WT1 DC vaccines (8-10 x 10\^6 cells in 500 μL saline solution with 5% human albumin) will be administered through intradermal injection at 5 sites (100 μL/site) in the ventromedial region of the upper arm (5-10 cm from the axillary lymph nodes). Injection sites will alternate between left and right arms. WT1/DC vaccines are administered every 2 weeks (+- 3 days) for a total of 6 administrations.

Also known as: IL15/IL15Ra/WT1 DC vaccine, IL15-transpresenting WT1-targeting DC vaccine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent (i.e. date of study entry (T0))
• Age ≥ 18 years at the time of signing informed consent
• Diagnosis with a histologically or cytologically confirmed solid tumor of the pancreas, esophagus, liver or ovaries that is advanced, recurrent or progressing after at least first-line anti-cancer treatment, or for which no alternative standard therapy is available due to intolerance to or refusal of standard-of-care treatment.
• Adequate hematological blood values following previous anti-cancer treatments, as judged by the Principal Investigator
• All treatment-related toxicities must have resolved to CTCAE grade ≤ 2 or must be stable and well controlled with minimal, local or non-invasive intervention, as judged by the Principal Investigator
• Reasonable life expectancy of at least 3 months, as estimated by the Principal Investigator
• At least 1 measurable or evaluable lesion as defined by the latest version of Immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) guidelines
• Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained at the time of screening:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500/µL) without granulocyte colony-stimulating factor support
• Lymphocyte count ≥ 0.5 x 109/L (500/µL)
• Platelet count ≥ 100 x 109/L (100,000/µL) without transfusion
• Hemoglobin ≥ 90 g/L (9 g/dL) (Patients may be transfused to meet this criterion)
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN), with the following exceptions:
• Patients with documented liver metastases: AST and ALT ≤ 5 x ULN
• Patients with documented liver or bone metastases: ALP ≤ 5 x ULN

You may not qualify if:

• Use of any investigational agent within 4 weeks before the planned day of leukapheresis
• Corticosteroid treatment within 1 week before leukapheresis, unless the Principal Investigator rationalizes otherwise
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover \< 10% of body surface area
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months
• Non-treated brain or meningeal mestases, or priorly treated brain or meningeal metastases with magnetic resonance imaging (MRI) evidence of progression in the last 8 weeks
• Pregnant or breastfeeding. Female subjects who are breastfeeding should discontinue nursing prior to the first dose of study treatment and until at least hundred days after the last study treatment administration
• Any other condition, either physical or psychological, or reasonable suspicion thereof on clinical or special investigation, which contraindicates the use of the vaccine, or may negatively affect patient compliance, or may place the patient at higher risk of potential treatment complications.

Sponsors & Collaborators

• University Hospital, Antwerp: lead
• Kom Op Tegen Kanker: collaborator
• Stichting tegen Kanker: collaborator

Study Sites (1)

Antwerp University Hospital

Edegem, 2650, Belgium

Location

Related Publications (2)

• Van den Bergh JM, Lion E, Van Tendeloo VF, Smits EL. IL-15 receptor alpha as the magic wand to boost the success of IL-15 antitumor therapies: The upswing of IL-15 transpresentation. Pharmacol Ther. 2017 Feb;170:73-79. doi: 10.1016/j.pharmthera.2016.10.012. Epub 2016 Oct 21.

  PMID: 27777088 BACKGROUND

• Van den Bergh J, Willemen Y, Lion E, Van Acker H, De Reu H, Anguille S, Goossens H, Berneman Z, Van Tendeloo V, Smits E. Transpresentation of interleukin-15 by IL-15/IL-15Ralpha mRNA-engineered human dendritic cells boosts antitumoral natural killer cell activity. Oncotarget. 2015 Dec 29;6(42):44123-33. doi: 10.18632/oncotarget.6536.

  PMID: 26675759 BACKGROUND

MeSH Terms

Conditions

Esophageal Neoplasms; Pancreatic Neoplasms; Ovarian Neoplasms; Liver Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Gonadal Disorders; Liver Diseases

Study Officials

• Timon Vandamme, MD

  University Hospital, Antwerp

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2023
• First Posted: July 27, 2023
• Study Start: December 6, 2023
• Primary Completion: September 28, 2025
• Study Completion: September 28, 2025
• Last Updated: April 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)