MK-3475 in Combination With MRI-guided Laser Ablation in Recurrent Malignant Gliomas
Summary
The blood brain barrier (BBB) is a major obstacle to drug delivery in the treatment of malignant brain tumors including glioblastoma multiforme (GBM). MRI-guided laser ablation (MLA) has been noted to disrupt peritumoral the blood brain barrier (BBB), which may then lead to increased access of new tumor antigens to the lymphovascular system and vice versa of immune effector cells to the tumor for effective activation of the immune system, and tumor infiltration, respectively. Therefore, the combination of MK-3475 and MLA as proposed in this protocol is hypothesized to create a therapeutic combinatorial effect in which MLA increases material access to promote immune activation and then MK-3475 maximizes these tumor-specific immune reactions to impart effective tumor control.
Timeline
- Start
- 2015-08-05
- Primary completion
- 2024-04-15
- Completion
- 2024-04-15
Outcome
Met primary endpoint
paper Median PFS was longer in LITT + PEM (4.5 versus 1.6 months; HR 0.21; 95% CI, 0.08-0.56; P = 0.0006). PMID 41748622 ↗
paper The pre-specified study endpoints were achieved. PMID 41748622 ↗
Publications
- Campian JL, Le SB, Ghiaseddin A, Butt OH, Manektalia H, Chen D, Xu Y, Liu J, Rahman M, Thai N, Leidig WA, Johanns T, Ansstas G, Zhou AY, Pugazenthi S, Dunn GP, Huang J, Chheda MG, Kim AH, Leuthardt EC, Tran DD. Laser interstitial thermal therapy and adjuvant pembrolizumab in recurrent high-grade astrocytoma: a Phase 1/randomized Phase 2b trial. Nat Commun. 2026 Feb 26;17(1):1763. doi: 10.1038/s41467-026-69522-w.
- Hwang H, Huang J, Khaddour K, Butt OH, Ansstas G, Chen J, Katumba RG, Kim AH, Leuthardt EC, Campian JL. Prolonged response of recurrent IDH-wild-type glioblastoma to laser interstitial thermal therapy with pembrolizumab. CNS Oncol. 2022 Mar 1;11(1):CNS81. doi: 10.2217/cns-2021-0013. Epub 2022 Jan 19.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Pembrolizumab | Monoclonal antibody | 100 mg | Intravenous |
| Subject | Pembrolizumab | Monoclonal antibody | 150 mg | Intravenous |
| Subject | Pembrolizumab | Monoclonal antibody | 200 mg | Intravenous |