Table 1.
Summary of completed and ongoing clinical trials on immune checkpoint inhibitors in mesothelioma.
| Clinical trial | Phase | Intervention | Target | Control group | Number | ORR | Survival (months) |
|---|---|---|---|---|---|---|---|
| Immune checkpoint inhibitors—monotherapy | |||||||
| MESOT-TREM-2008 (NCT01649024) | II | Tremelimumab | CTLA-4 | None | 29 | 7% | PFS 6.2, OS 10.7 |
| MESOT-TREM-2012 (NCT01655888) | II | Tremelimumab | CTLA-4 | None | 29 (Est) | 3.4% | PFS 6.2, OS 11.3 |
| DETERMINE (NCT01843374) | IIb | Tremelimumab | CTLA-4 | Placebo | 571 | NA | OS (treated group 7.7; placebo group 7.3) |
| KEYNOTE-028 (NCT02054806) | Ib | Pembrolizumab | PD-1 | None | 477 | 20% | PFS 5.4; OS 18 |
| NCT02399371 | II | Pembrolizumab | PD-1 | None | 65 | pleural 20%, peritoneal 12.5% | PFS 4.5, OS 11.5 |
| PROMISE-meso (NCT02991482) | III | Pembrolizumab | PD-1 | Drug vs. gemcitabine or vinorelbine | 144 | treatment 22%, chemotherapy 6% | PFS (treatment 2.5, chemotherapy 3.4) OS (treatment 10.7, chemotherapy 11.7) |
| NCT02784171 | II/III | Pembrolizumab | PD-1 | Drug + pemetrexed/cisplatin vs pemetrexed/cisplatin | 126 (Est) | NA: recruiting | |
| NCT04056026 | I | Pembrolizumab + faecal microbiota transplant | PD-1 | 1 | NA | ||
| NCT02959463 | I | Pembrolizumab + radiation therapy | PD-1 | Hemithoracic radiation therapy + pembrolizumab; palliative radiotherapy + pembrolizumab | 24 (Est) | NA: recruiting | |
| NCT02707666 | I | Pembrolizumab | PD-1 | Drug + surgery + pemetrexed/cisplatin | 15 (Est) | NA: recruiting | |
| NIVOMES (NCT02497508) | I | Nivolumab | PD-1 | None | 33 | 24% | PFS 2.6; OS 11.8 |
| MERIT (JapicCTI-163247) | II | Nivolumab | PD-1 | None | 34 | 29% | PFS 6.1; OS 17.3 |
| CONFIRM (NCT03063450) | III | Nivolumab | PD-1 | Control | 336 (Est) | NA: recruiting | |
| JAVELIN (NCT01772004) | Ib | Avelumab | PD-L1 | None | 1758 | 9% | PFS 4.1; OS 10.7 |
| NCT03399552 | I/II | Avelumab + Stereotactic Body Radiation Therapy | PD-L1 | None | 27 (Est) | NA: recruiting | |
| DREAM | II | Durvalumab | PD-L1 | Drug + pemetrexed & cisplatin + maintenance | 54 | 48% (mRECIST) or 50% (iRECIST) | PFS 6.9 |
| NCT02899195 | II | Durvalumab | PD-L1 | Drug + pemetrexed/ cisplatin vs concurrent + maintenance | 55 | NA: active, non-recruiting | |
| NCT03228537 | I | Atezolizumab | PD-L1 | Neoadjuvant + maintenance drug + surgery | 28 (Est) | NA: recruiting | |
| Combined immune checkpoint inhibitors | |||||||
| NCT02141347 | I | Tremelimumab + Durvalumab | CTLA-4/PD-L1 | None | 65 | ||
| NIBIT-MESO-1 (NCT02588131) | II | Tremelimumab + Durvalumab | CTLA-4/PD-L1 | None | 40 | 28% | PFS 5.7; OS 16.6 |
| NCT03075527 | II | Tremelimumab + Durvalumab | CTLA-4/PD-L1 | None | 19 | 5% | PFS 2.8; OS 7.8 |
| NCT02592551 | II | Tremelimumab + Durvalumab | CTLA-4/PD-L1 | Durvalumab, durvalumab + tremelimumab, vs placebo | 20 | NA: active, non-recruiting | |
| INITIATE (NCT03048474) | II | Ipilimumab + nivolumab | CTLA-4/PD-1 | None | 36 | 29% | PFS 6.2 |
| MAPS-2 (NCT02716272) | II | Ipilimumab + nivolumab | CTLA-4/PD-1 | Nivolumab vs nivolumab + ipilimumab | 125 | single 19%, dual 28% | PFS (single 4.0, dual 5.6) OS (single 11.9, dual 15.9) |
| Checkmate743 (NCT02899299) | III | Ipilimumab + nivolumab | CTLA-4/PD-1 | Combination vs pemetrexed/cisplatin | 606 | NA: active, non-recruiting | |
| Multimodal immunotherapy | |||||||
| NCT03393858 | I/II | Autologous DCs + pembrolizumab + hyperthermia | PD-1 | 40 (Est) | NA: recruiting | ||
| MESOVAX (NCT03546426) | I | Autologous DCs + pembrolizumab | PD-1 | Autologous DCs + pembrolizumab + IL-2 | 18 (Est) | NA: not yet recruiting | |
| NCT04040231 | I | Targeted cancer vaccine (WT1) + nivolumab | WT1/PD-1 | 10 (Est) | NA: recruiting | ||
| NCT03126630 | I/II | Anetumab ravtansine + Pembrolizumab | MSLN/PD-1 | Pembrolizumab vs pembrolizumab + anetumab ravtansine | 134 (Est) | NA: recruiting | |
| NCT03644550 | II | LBM-100 + pembrolizumab | MSLN/PD-1 | None | 38 (Est) | NA: recruiting | |
| NCT03175172 | II | CRS-207 + Pembrolizumab | MSLN/PD-1 | None | 10 | Terminated (low enrolment; lack of clinical activity) | |
| NCT02758587 | I/II | Defactinib + pembrolizumab | FAK/PD-1 | None | 59 (Est) | NA: recruiting | |
| NCT02414269 | I | anti-MSLN CAR T cells + pembrolizumab | MSLN/PD-1 | Drug + cyclophosphamide vs drug + pembrolizumab | 66 (Est) | 2/14 CR & 5/14 PR | |
| NCT03074513 | II | Atezolizumab + Bevacizumab | PD-L1/VEGF | None | 160 (Est) | NA: recruiting | |
Figures for survival (in months) are represented by median values unless otherwise stated. ORR assessment criteria include the modified Response Evaluation Criteria in Solid Tumours for MPM (mRECIST) or RECIST modified for immunotherapy (iRECIST).
CR complete response, CTLA-4 cytotoxic T-lymphocyte-associated protein 4, DC dendritic cell, FAK focal adhesion kinase, IL-2 interleukin-2, MSLN mesothelin, NA not available, ORR overall response rate, OS overall survival, PD-1 programmed cell death protein 1, PD-L1 programmed death ligand 1, PFS progression-free survival, PR partial response, VEGF vascular endothelial growth factor, WT1 Wilms’ tumour.