Abstract
BACKGROUND: Recurrent high-grade glioma (rHGG) lacks effective life-prolonging treatments and the efficacy of systemic PD-1 and CTLA-4 immune checkpoint inhibitors is limited. The multi-cohort Glitipni phase I trial investigates the safety and feasibility of intraoperative intracerebral (iCer) and postoperative intracavitary (iCav) nivolumab (NIVO) ± ipilimumab (IPI) treatment following maximal safe resection (MSR) in rHGG. MATERIALS AND METHODS: Patients received 10 mg IV NIVO within 24 h before surgery, followed by MSR, iCer 5 mg IPI and 10 mg NIVO, and Ommaya catheter placement in the resection cavity. Biweekly postoperative iCav administrations of 1-5-10 mg NIVO (cohort 4) or 10 mg NIVO plus 1-5-10 mg IPI (cohort 7) were combined with 10 mg IV NIVO for 11 cycles. RESULTS: 42 rHGG patients underwent MSR with iCer NIVO + IPI. 16 pts were treated in cohort 4 (postoperative iCav NIVO at escalating doses) while 28 patients were treated in cohort 7 (intra and postoperative iCav NIVO and escalating doses of IPI). The most common TRAE was fatigue; no grade 5 AE occurred. Dose-limiting toxicity was grade 3 neutrophilic pleocytosis (4 pts) receiving iCav NIVO plus 5 or 10 mg IPI. PFS and OS did not significantly differ between cohorts (median OS: 42 [95% CI 26-57] vs. 35 [29-40] weeks; 1-year OS rate: 37% vs. 29%). Baseline B7-H3 expression significantly correlated with worse survival. OS compared favorably to a historical pooled cohort (n = 469) of Belgian rHGG pts treated with anti-VEGF therapies (log-rank P = .015). CONCLUSION: Intraoperative iCer IPI + NIVO with postoperative iCav NIVO ± IPI up to biweekly doses of 1 mg IPI + 10 mg NIVO is feasible and safe, showing encouraging OS in rHGG patients. ClinicalTrials.gov registration: NCT03233152.