NCT05765084

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: University Hospital, Antwerp · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Malignant pleural mesothelioma (MPM) is a highly aggressive and in virtually all cases fatal cancer that is tightly associated with prior asbestos exposure. Despite some improvement over time, the prognosis of patients diagnosed with MPM remains dismal with a median overall survival from diagnosis of only 9-16 months. In this single arm phase I/II trial the investigators want to demonstrate the feasibility and safety of integrating the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab and WT1-targeted dendritic cell vaccination in epitheloid MPM patients in conjunction with first line platinum/pemetrexed-based chemotherapy. In addition, chemo-immunotherapy-induced immunogenicity will be studied and patient's clinical outcome will be documented for comparison with current patient's outcome allowing indication of the added value. Fifteen patients diagnosed with histologically proven epithelial MPM (stage I-IV) will be included. Patients should be able to undergo leukapheresis, chemotherapy and immunotherapy. Patients who underwent prior treatment for MPM or with a history of another malignancy within the last three years will be excluded. The intention of this study is to administer four 3-weekly (±3 days) platinum/pemetrexed-based chemotherapy cycles (CT1-4) combined with atezolizumab treatments (A1-4) and autologous WT1 messenger (m)RNA-loaded dendritic cells (V1-4) at day 0 and day 14 (±3 days) of each chemotherapy cycle, respectively. Additional atezolizumab doses and/or WT1/DC vaccines after the chemo-immunotherapy study scheme can be administered to the patient if consent for continuation of atezolizumab treatment and/or WT1/DC vaccination was obtained and residual WT1/DC vaccine aliquots are available. In that case, atezolizumab and/or WT1/DC vaccines will be administered on a 4-weekly basis (±1 week). The WT1/DC vaccines will be administered within 1 week after atezolizumab administration. After the final WT1/DC vaccination and/or atezolizumab administration, patients will enter a follow-up phase that lasts for up to 90 days after final WT1/DC vaccination and/or atezolizumab administration or 24 months after diagnosis, whichever occurs later.

Conditions

• Malignant Pleural Mesothelioma

Interventions

Type	Name	Description
BIOLOGICAL	Dendritic 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).
DRUG	Atezolizumab	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.
DRUG	Platinum/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.

Timeline

• Start date: 2023-02-24
• Primary completion: 2026-10-01
• Completion: 2026-10-01
• First posted: 2023-03-13
• Last updated: 2024-05-16

Locations

3 sites across 1 country: Belgium