Atim-07. Window-of-opportunity Clinical Trial of Pembrolizumab in Recurrent Glioblastoma Patients
Year: 2018
Type: conference-abstract
Abstract: A window-of-opportunity trial was used to ascertain the immune modulatory properties of pembrolizumab in recurrent GB patients. In an open label, single-center, single-arm Phase 2 trial, 15 patients with recurrent GBM, were treated with up to two doses of pembrolizumab prior to surgery and afterwards received pembrolizumab until disease progression or the development of unacceptable toxicities. The co-primary objectives of the study were to evaluate immune effector function in resected GBM tissue and to determine progression free survival at 6 months (PFS6). We screened 21 patients, of whom 15 were enrolled and received at least one dose of pembrolizumab. The most common adverse event was grade 1 or 2 fatigue in 40% of patients followed by headache in 27%. There were five grade 3 or 4 adverse events including one with cerebral edema requiring surgery. There were no treatment-related deaths; 5 (33%) of 15 patients died because of progression of disease. The median follow-up time for all patients was 12 months (95% CI3-31). Based on iRANO, 10 patients had progressive disease, 3 had a partial response and 1 had stable disease. The longest ongoing duration of response exceeded 34 months in two patients. Median PFS was 7 months (95% CI 4–16) and PFS6 was 53% (95% CI 33%-86%). Median OS was not reached (95% CI 15 to not reached), with an estimated 1-year overall survival of 72% (52%–99.6%). CyTOF and IHC immune analysis revealed that GBM tumors were markedly enriched with CD68+ macrophages but had a paucity of effector T cells. Although pembrolizumab was well tolerated, a high predominance of immunosuppressive CD68+ myeloid cells and a marked scarcity of T cells within the tumor microenvironment may be limiting the activity of PD-1 blockade.
Source: Neuro-Oncology
Authors: John de Groot, Marta Penas-Prado, Jacob Mandel, Barbara O’Brien, Shiao-Pei Weathers, Monica Loghin, Carlos Kamiya-Matsuoka, Shouhao Zhou, Rivka Colen, Kathy Hunter, Gregory Fuller, Jason T Huse, Ganesh Rao, Jeffrey Weinberg, Sujit Prabhu, Sherise Ferguson, Ying Yuan, Luis Vence, James Allison, Padmanee Sharma, Amy Heimberger
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2899840191