Table 1.
Recent clinical trials for TME-targeted therapy of LCBM.
| Agents | Histology | Phase | Purpose | Status/outcome | Reference or http://clinicaltrials.gov identifier |
| Durvalumab | NSCLC | 2 | To assess the efficacy of durvalumab combined with radiation therapy in LCBM | No yet recruiting | NCT04889066 |
| Pembrolizumab | NSCLC | 2 | To determine the safety of three different stereotactic radiosurgery (SRS) radiation arms in combination with pembrolizumab in melanoma or NSCLC-associated BMs | Recruiting | NCT02858869 |
| GRN1005 | NSCLC | 2 | To assess the efficacy and safety of GRN1005 in LCBM | CR or PR: ≥30% decrease in the largest diameter of target lesions | NCT01497665 |
| Atezolizumab | SCLC | 2 | To assess the efficacy of chemotherapy and atezolizumab in LCBM | Recruiting | NCT04610684 |
| Pembrolizumab | NSCLC | 2 | To evaluate whether pembrolizumab prolongs survival and preserves quality of life in LCBM patients | Not yet recruiting | NCT04964960 |
| Bevacizumab | Non-squamous NSCLC | 2 | To assess the efficacy of bevacizumab in combination with first- or second-line therapy in LCBM | OS: 12.1 (10.3–14.9) months | NCT00312728 |
| Pembrolizumab+bevacizumab | NSCLC | 2 | To study the activity of pembrolizumab in combination with bevacizumab in LCBM | Recruiting | NCT02681549 |
| MK-3475 | NSCLC | 2 | To assess the activity of MK-3475 in untreated melanoma or NSCLC-associated BMs | 11 (11/42) patients showed better response | NCT02085070 |
| Pembrolizumab | NSCLC | 2 | To determine the activity of PD-1 blockade in the CNS | Pembrolizumab has activity in brain metastases from NSCLC with PD-L1 expression at least 1% | [94,95] |
| Nivolumab | Non-squamous NSCLC patients | EAP | To evaluate nivolumab efficacy and safety in LCBM | Nivolumab is active in non-squamous NSCLC patients with BM | [96] |
| Immune checkpoint inhibitor | NSCLC | Retrospective | To evaluate outcomes of LCBM patients treated with checkpoint inhibitors | In multivariate analysis, BMs are not associated with a poorer survival in patients with ICI-treated NSCLC | [97] |
BM: Brain metastasis; CNS: Central nervous system; CR: Complete response; EAP: Expanded access programs; ICI: Immune checkpoint inhibitor; LCBM: Lung cancer brain metastasis; NSCLC: Non-small cell lung cancer; OS: Overall survival; PD-1: Programmed cell death-1; PD-L1: Programmed cell death-Ligand 1; PR: Partial response; SCLC: Small cell lung cancer; SRS: Stereotactic radiosurgery; TME: Tumor microenvironment.