Skip to main content

Table 1 Clinical trials in MPM of checkpoint inhibitors in the surgical setting (Neo-adjuvant and post-surgery)

From: Emerging avenues in immunotherapy for the management of malignant pleural mesothelioma

Trial acronym or title Trial identifier Treatment Phase Primary objective(s) Completion date Report status References
A Pilot Window-of-opportunity Study of the Anti-PD-1 Antibody Pembrolizumab in Patients With Resectable Malignant Pleural Mesothelioma NCT02707666 Neoadjuvant pembrolizumab every 21 days for three cycles
A PET/CT scan will then assess response to Pembrolizumab followed by surgical resection followed by adjuvant chemotherapy with cisplatin and pemetrexed every 21 days for 4 cycles
I The primary objective is to assess an increase in interferon-γ, measured via a gene expression profile (GEP), comparing matched pre- and post-treatment samples (IFN-G GEP response), and other correlative analyses will be performed to identify additional candidate biomarkers for benefit or inherent resistance to Pembrolizumab Estimated Primary Completion Date December 20, 2022
Estimated Study Completion Date December 20, 2025
Interim [46]
Phase I Trial of Adjuvant Pembrolizumab After Radiation Therapy for Lung-Intact Malignant Pleural Mesothelioma NCT02959463 Cohort 1: Hemi-thoracic radiation therapy, plus intravenous Pembrolizumab repeated every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity
Cohort 2: Palliative radiation therapy over 1–3 weeks followed by intravenous Pembrolizumab similar to cohort 1. After completion of treatment, patients will be followed up at 30 days, every 6 weeks for 48 weeks, then every 12 weeks for up to 5 years
I To determine the safety and tolerability of pembrolizumab administered after radiation therapy in patients with malignant pleural mesothelioma (MPM) who have not undergone extra-pleural pneumonectomy Estimated Primary Completion Date May 31, 2020
Estimated Study Completion Date May 31, 2021
Interim [47]
A Feasibility Trial of Neoadjuvant Cisplatin-Pemetrexed With Atezolizumab in Combination and in Maintenance for Resectable Malignant Pleural Mesothelioma NCT03228537 Neoadjuvant cisplatin-pemetrexed disodium (pemetrexed)-atezolizumab
Surgical resection (extra-pleural pneumonectomy EPP, or pleurectomy with decortication P/D), followed finally by radiotherapy for those patients who underwent EPP. Maintenance atezolizumab will then be given for up to 1 year in the absence of disease progression or unexpected toxicity
I To evaluate if the regimen of neoadjuvant cisplatin-pemetrexed disodium (pemetrexed)-atezolizumab, surgery ± radiation, then maintenance atezolizumab is feasible and safe for patients with resectable malignant pleural mesothelioma Estimated Primary Completion Date June 1, 2021
Estimated Study Completion Date June 1, 2021
Interim [38]
Window Of Opportunity Phase II Study Of MEDI4736 Or MEDI4736 + Tremelimumab In Surgically Resectable Malignant Pleural Mesothelioma NCT02592551 Durvalumab (anti-PD-L1) or combination therapy with Durvalumab plus tremelimumab (anti-CTLA4) in mesothelioma patients undergoing surgery II Primary outcome measures are assessment of the intra-tumoral ratio of CD8 T cells to regulatory T cells (CD8/Treg), the percentage of inducible T-cell co-stimulator (ICOS) + CD4 T cells, and the tumor expression programmed death-ligand 1 (PD-L1) Estimated Primary Completion Date September 1, 2022
Estimated Study Completion Date September 1, 2022
Interim [47]
Neoadjuvant Immune Checkpoint Blockade in Resectable Malignant Pleural Mesothelioma NCT03918252 Cohort 1: Preoperative nivolumab, prior to planned surgery
Cohort 2: Preoperative nivolumab + ipilimumab prior to planned surgery
I/II Safety and Feasibility of neoadjuvant nivolumab ± ipilimumab in patients with resectable MPM Estimated Primary Completion Date June 2025
Estimated Study Completion Date June 2026
  [48, 49]
NICITA:
Nivolumab With Chemotherapy in Pleural Mesothelioma After Surgery
NCT04177953 Following cytoreductive surgery (with or without hyperthermic intrathoracic chemoperfusion) patients will be randomized to receive either platinum-based adjuvant chemotherapy (Arm A) or platinum-based adjuvant chemotherapy together with nivolumab (Arm B) II The primary endpoint will be time-to-next-treatment (TNT) which has been defined as the time from randomization until the initiation of any additional intervention as a consequence of disease progression, using a Kaplan–Meier analysis Estimated Primary Completion Date July 2023
Estimated Study Completion Date December 2023
Interim [50]