First-line immunotherapy using Wilms’ tumor protein 1 (WT1)-targeted dendritic cell vaccinations for malignant pleural mesothelioma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Antwerp University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Neoplasms [C04], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

3 Oct 2017 → 9 Mar 2025

Decision date (initial)

2024-11-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-517970-35-00

EudraCT number

2014-001099-75

ClinicalTrials.gov

NCT02649829

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To evaluate the feasibility and safety of Wilms' tumor 1 mRNA-electroporated dendritic cell (DC) vaccinations in patients with malignant pleural mesothelioma (MPM) as first-line treatment combined with standard chemotherapy

Secondary objectives 2

1. Clinical objective - To assess the time to progression (TTP) and progression-free survival (PFS) after chemoimmunotherapy with or without pleurectomy/decortication (P/D) and to assess overall survival (OS) from diagnosis and start of treatment
2. Translational objective - To determine the in vivo systemic and local immunogenicity of WT1-targeted DC vaccination when combined with chemotherapy as treatment of MPM

Conditions and MedDRA coding

Malignant Pleural Mesothelioma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Diagnosis with histologically proven epithelial MPM
2. Age: ≥18 years at the time of enrollment
3. WHO performance status 0–1 at the time of enrollment
4. Fit to undergo general anesthesia, a thoracoscopy, leukapheresis, chemotherapy, immunotherapy and (in case of resectable disease) P/D
5. No history of receiving any investigational treatment within 28 days of study enrollment
6. No history of intolerance to pemetrexed and/or cisplatin
7. Before patient registration written informed consent must be given according to ICH/GCP, and national/local regulations

Exclusion criteria 6

1. Unwilling or unable to comply with the study requirements
2. Prior treatment for mesothelioma
3. History of other malignancy within the last five years, except for non-melanoma skin cancer and cervical carcinoma in situ or unless the investigator rationalizes otherwise
4. Known proven metastases
5. Known concomitant presence of any immunosuppressive disease (e.g. HIV) or any active autoimmune condition, except for vitiligo
6. Pregnant or breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Safety will be assessed by clinical laboratory tests and adverse event reporting: (1) Microbiological testing (bacteria, fungi, mycoplasma, endotoxin) will be performed to assess safe DC vaccine production, (2) Local toxicity (e.g. skin reactions at injection site) will be reported, (3) Systemic toxicity will be scored according to the latest version of the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicity Criteria (CTC)
2. Feasibility will be assessed based on the success of (1) leukapheresis and (2) DC vaccine preparation (production of at least 4 DC vaccines) and (3) administration of combined chemoimmunotherapy cycles within the proposed time schedule

Secondary endpoints 2

1. Clinical endpoints: time to progression (TTP), progression-free survival (PFS) and overal survival (OS) (Tumor assessment will be performed according to the latest modified Response Evaluation Criteria In Solid Tumors (RECIST), PET Response Criteria In Solid Tumors (PERCIST) and endpoints for cancer immunotherapy trials)
2. Translational endpoint: immunological responses (Systemic and local immunological response analysis will be performed to determine the in vivo immunogenicity of WT1 mRNA-electroporated DC vaccinations when combined with chemotherapy for the frontline treatment of MPM by evaluating the development of effective anti-mesothelioma immunity)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Antwerp University Hospital

Sponsor organisation

Antwerp University Hospital

Address

Drie Eikenstraat 655

City

Edegem

Postcode

2650

Country

Belgium

Scientific contact point

Organisation

Antwerp University Hospital

Contact name

Center for Cell Therapy and Regenerative Medicine

Public contact point

Organisation

Antwerp University Hospital

Contact name

Center for Cell Therapy and Regenerative Medicine

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications