RecruitingPhase 1Phase 2NCT05765084

Integration of the PD-L1 Inhibitor Atezolizumab and WT1/DC Vaccination Into Platinum/Pemetrexed-based First-line Treatment for Epithelioid Malignant Pleural Mesothelioma

Sponsor

University Hospital, Antwerp

Enrollment

15 participants

Start Date

Feb 24, 2023

Study Type

INTERVENTIONAL

Conditions

Malignant Pleural Mesothelioma

Summary

In this multicenter phase I/II trial, the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab and dendritic cells (DCs) loaded with the mesothelioma-associated tumor antigen WT1 will be integrated into platinum/pemetrexed-based first-line chemotherapy for the treatment of epitheloid malignant pleural mesothelioma (MPM). The general objective is to provide the first-in-human experimental demonstration that the combination of platinum/pemetrexed-based chemotherapy with atezolizumab and WT1/DC vaccination is feasible and safe, has clinical activity and enables the induction of mesothelioma-specific immune responses in patients with MPM.

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This trial is testing a combination of immunotherapy (atezolizumab), a personalized cancer vaccine (WT1/DC vaccine), and standard chemotherapy (platinum and pemetrexed) as first-line treatment for people with epithelioid malignant pleural mesothelioma — a rare cancer of the lining around the lungs, often linked to asbestos exposure. **You may be eligible if...** - You are 18 or older - You have been diagnosed with epithelioid mesothelioma (confirmed by biopsy) that cannot be surgically removed (any stage) - You have not received prior treatment for mesothelioma - Your overall health is good (WHO performance status 0–1) - Your blood counts and organ function meet the required thresholds **You may NOT be eligible if...** - You have received prior chemotherapy or immunotherapy for mesothelioma - You have active autoimmune disease requiring systemic treatment - You have serious infections (including uncontrolled HIV or hepatitis B/C) - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

BIOLOGICALDendritic cell vaccination

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 on day 14 of each 3-weekly platinum/pemetrexed-based chemotherapy cycle. Additional WT1/DC vaccinations after the study treatment schedule can be administered (optional) at 4-weekly intervals (± 1 week).

DRUGAtezolizumab

Atezolizumab (1200 mg) will be administered on day 0 of each 3-weekly platinum/pemetrexed-based chemotherapy cycle. Atezolizumab should be administered before chemotherapy administration as an IV infusion over 60 (±15) minutes. If the first infusion is tolerated, all subsequent infusions may bedelivered over 30 (±10) minutes. Additional atezolizumab treatment (1680 mg) after the study treatment schedule can be administered (optional) at 4-weekly intervals (± 1 week) as an IV infusion over 30-60 minutes.

DRUGPlatinum/pemetrexed based chemotherapy

On the first day of each cycle (day 0), pemetrexed 500 mg/m2 should be administered as intravenous (IV) infusion over 10 minutes, followed by cisplatin 75 mg/m2 as IV over approximately 2 hours. The actual doses of the drugs to be administered to patients will be determined by calculating the patient's body surface area at the beginning of each cycle. For ease of dose administration, the protocol allows ± 5% variance in the calculated total dose per infusion. If deemed necessary, the treating physician can decide to replace cisplatin by carboplatin. In that case, carboplatin will be delivered to an area under the concentration-time curve (AUC) of 5 as an IV infusion over 1 hour.