Integration of the PD-L1 inhibitor atezolizumab and WT1/DC vaccination into platinum/pemetrexed-based first-line treatment for epithelioid 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], Phenomena and Processes [G] - Immune system processes [G12], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Diseases [C] - Neoplasms [C04]

Trial duration

24 Feb 2023 → ongoing

Decision date (initial)

2024-11-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-515293-27-00

EudraCT number

2021-003229-31

ClinicalTrials.gov

NCT05765084

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To investigate the feasibility and safety of adding atezolizumab and WT1/DC vaccination to first-line platinum/pemetrexed-based chemotherapy in patients with epithelioid MPM

Secondary objectives 2

1. To assess indicators of clinical activity of first-line platinum/pemetrexed-based chemotherapy when combined with atezolizumab and WT1/DC vaccination in epithelioid MPM patients
2. To determine the immunogenicity of atezolizumab and WT1/DC vaccination when added to first-line platinum/pemetrexed-based chemotherapy in epithelioid MPM patients

Conditions and MedDRA coding

Malignant pleural mesothelioma, epithelioid subtype (stage I-IV)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Signed informed consent
2. Diagnosis with histologically proven epithelioid unresectable MPM (stage I-IV)
3. Aged ≥18 years at the time of signing the informed consent form
4. World Health Organization (WHO) performance status: grade 0-1
5. Adequate hematologic and end-organ function
6. Negative viral serology for Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV)
7. Willing and able to comply with the study protocol, as judged by the treating physician
8. Women of childbearing potential must have a negative serum or urine pregnancy test at the time of screening

Exclusion criteria 11

1. History of another malignancy within the last three years (except for malignancies with a negligible risk of metastasis or death)
2. Symptomatic, untreated, or actively progressing central nervous system metastases
3. Active or history of autoimmune disease or immune deficiency
4. Severe infection within 4 weeks prior to initiation of study treatment
5. Prior treatment for MPM
6. Prior allogeneic stem cell or solid organ transplantation
7. Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
8. Use of any investigational agent within 28 days before study enrollment
9. Recent treatment with systemic immunostimulatory agents or systemic immunosuppressive medication
10. Pregnant or breastfeeding
11. Any other condition, either physical or psychological, or reasonable suspicion thereof on clinical or special investigation, which contraindicates the use of atezolizumab, pemetrexed, cisplatin/carboplatin and/or WT1/DC vaccines, or may negatively affect patient compliance, or may place the patient at higher risk of potential treatment complications

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Feasibility: the proportion of patients who completed study treatment schedule (i.e. administration of four platinum/pemetrexed-based chemotherapy cycles in combination with four atezolizumab treatments and four WT1/DC vaccinations
2. Safety, based on the occurrence of reported AEs and SAEs during investigational treatment administration and during follow-up: (A) Proportions of patients that experienced (S)AEs possibly, probably or definitely related to pemetrexed and/or cisplatin/carboplatin and/or atezolizumab and/or WT1/DC vaccination (B) Number and grade of AEs and SAEs

Secondary endpoints 2

1. Clinical efficacy, including: (A) Best overall response (BOR), duration of response (DOR), disease control rate (DCR), objective response rate (ORR) and progression free survival (PFS), (B) Overall survival (OS)
2. Immunogenicity: Functional WT1-specific T cell responses

Investigational products

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

Test 3

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 · 3 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

Documents 6 files

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

Application history

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