ATIM-10. PHASE I/II TRIAL OF RADIATION THERAPY, TEMOZOLOMIDE AND PEMBROLIZUMAB FOLLOWED BY TEMOZOLOMIDE AND PEMBROLIZUMAB IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Abstract

BACKGROUND: Patients with glioblastoma (GBM) have a poor prognosis despite maximal resection, and standard of care radiation (RT) with temozolomide (TMZ) [SOC]. Immune checkpoint inhibitors have shown antitumor activity in solid tumors and Hodgkin’s lymphoma. GBM have been shown to express programmed cell death ligand-1 (PD-L1) with anti-tumor activity demonstrated in animal models. A single arm phase I/II trial was done to determine the safety and efficacy of pembrolizumab (anti PD-1 monoclonal antibody) in combination with SOC in newly diagnosed GBM patients. Phase I data are presented.METHODS: Standard adult eligibility criteria were used but > 25% resection was required. Patients received pembrolizumab (200mg intravenously every 3 weeks) starting on day 1 of RT+TMZ with plans for dose de-escalation if a DLT occurred in cohort 1. The DLT window was 9 weeks from the start of RT. Treatment then consisted of pembrolizumab every 3 weeks along with TMZ (9 week cycles). The primary endpoint was maximum tolerated dose (MTD) and determine the recommended phase 2 dose (RP2D).RESULTS: Four patients with GBM were treated (3 men, 1 woman). Median age was 64 (range 39–67) and median KPS was 90 (range 80–100). The most common toxicities were leukopenia (grade 2, n = 2; grade 1, n = 2), anemia (grade 1, n = 4), and fatigue (grade 1, n = 2). There were no grade 3 or 4 toxicities or interruptions in treatment. One patient withdrew without toxicity. The remaining 3 patients are alive and still on treatment having completed 3, 2, and 1 cycles post-RT thus far.CONCLUSION: The combination of pembrolizumab at 200mg added to SOC in patients with newly diagnosed GBM seems to be tolerable. No immune related adverse events were seen in 4 subjects receiving the combination. The RP2D is 200mg every three weeks.