Atim-17. Early Results of a Multicenter Phase I and Open-label, Randomized Phase Ii Study Testing the Toxicities and Efficacy of Mk-3475 (pembrolizumab) in Combination With Mri-guided Laser Interstitial Thermal Therapy (litt) in Recurrent Malignant Gliomas
Year: 2017
Type: article
Abstract: LITT was recently demonstrated to induce temporary blood-brain barrier disruption, possibly allowing bilateral trafficking of tumor neoantigens and immune cells to induce glioma-specific immune activation - a phenomenon akin to in situ tumor vaccination. We hypothesize that combining LITT with immune checkpoint inhibition will create a synergistic therapy for recurrent GBM. The phase 1 study is a standard 3x3 design with a maximum of 18 patients with bevacizumab-naïve recurrent WHO grade 3–4 glioma. The primary endpoint is safety and toxicity of LITT plus pembrolizumab at 100, 150, or 200mg IV q3weeks. Phase 2 includes 40 patients with bevacizumab-naïve recurrent GBM, equally randomized to either pembrolizumab alone or LITT plus pembrolizumab. The primary endpoint is PFS. Serial immunophenotyping will be performed to evaluate potential positive synergy between LITT and pembrolizumab. Phase 1 accrual was completed with 9 patients (3 at each pembrolizumab dose level). Two had recurrent anaplastic astrocytoma and 7 recurrent GBM. As of 5/16/17, there was no dose-limiting toxicity with pembrolizumab 200mg IV q3weeks. The median number of doses given per patient was 5 (range 2 to 12). Severe adverse events possibly related to the study treatment included a grade 3 rash and diarrhea in 1 patient (11%) and grade 3 pneumonitis and hypotension in another patient (11%). No grade 3/4 intracranial edema deemed related to study treatment was observed. Best response was stable disease. One (11%), 2 (22%), and 1 (11%) GBM patients have not progressed for 20.7, 8, and 4 months, respectively. One (11%) anaplastic astrocytoma patient has not progressed for 12 months. LITT plus pemprolizumab 200mg IV q3weeks is generally well tolerated in patients with recurrent high-grade glioma. Prolonged PFS was observed in several patients. Updated study data will be presented. The study should proceed to the planned phase 2.
Source: Neuro-Oncology
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2767299400