Atim-29. Nrg Bn002: Safety Data From a Phase I Study of Ipilimumab (ipi), Nivolumab (nivo), and the Combination for Newly Diagnosed Glioblastoma (gbm)
Year: 2018
Type: conference-abstract
Abstract: INTRODUCTION: Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in several solid tumors including brain metastases, but single agent ICIs have failed to improve outcome in recurrent (GBM). This study evaluated the safety of anti-CTLA-4 (IPI) and anti-PD-1 (NIVO) ICIs alone or in combination in newly diagnosed GBM during adjuvant temozolomide (TMZ) treatment. This phase I study evaluated IPI (3mg/kg), NIVO (3mg/kg), and the combination (1 mg/kg & 3 mg/kg respectively) followed by an expansion cohort for the combined treatment of adults with unifocal, supratentorial newly diagnosed GBM after gross or near total resection. ICIs were given with adjuvant TMZ. The primary endpoint was the dose limiting toxicity (DLT) within 8 weeks of starting ICIs. A standard up-and-down design was used with 6 evaluable patients enrolled at a given dose level; safety defined as 1 or fewer patients with DLTs. Thirty-two patients (31 analyzable; 1 not treated) were enrolled, 6 to each arm and 14 to the expansion cohort. Median age: 54 years (range: 23–74), 68% male and 84% white. Overall, treatment was well tolerated with a 16% rate of Grade 4 events; without increased toxicity of combination ICIs; there were no Grade 5 events. One DLT was seen in each single-agent arm; none in the combination arm. Median follow-up time was 8.4 months (range: 0.5–23.6), 10 had progressed (32%) and 8 had died (26%), 7 due to disease progression and 1 due to pulmonary embolism. IPI and NIVO are safe and tolerable with similar toxicity profiles noted with other cancers when given with adjuvant TMZ for newly diagnosed GBM. Combination IPI+NIVO is not more toxic than single agents. These results provide necessary safety data for a subsequent efficacy trial to test the combination of ICIs in newly diagnosed GBM. Funding: U10CA180868 and U10CA180822 (NCI).
Source: Neuro-Oncology
Institutions: National Institutes of Health, National Cancer Institute, Center for Cancer Research, NRG Oncology, University Hospitals of Cleveland, University Hospitals Cleveland Medical Center, Harvard University, Dana-Farber Cancer Institute, University of California, San Francisco, Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center, The Ohio State University, Emory University, The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2900088538