Atim-35. Results of the Phase Ib Keynote-028 Multi-Cohort Trial of Pembrolizumab Monotherapy in Patients With Recurrent Pd-L1-Positive Glioblastoma Multiforme (Gbm)

Patients with recurrent GBM have limited treatment options and poor clinical outcome. Tumors, including GBM, use the PD-1 pathway to evade immune responses. KEYNOTE-028 (NCT02054806) evaluated the safety and efficacy of the anti–PD-1 monoclonal antibody pembrolizumab in 20 advanced solid tumor types. Results of the GBM cohort (N=26) are presented. Key inclusion criteria included advanced (unresectable and/or metastatic) bevacizumab-naive GBM, failure of or inability to receive standard therapy, ECOG PS 0-1, and PD-L1 expression in ≥1% of tumor or stroma cells by immunohistochemistry. Patients received pembrolizumab 10 mg/kg every 2 weeks for up to 24 months or until confirmed progression, intolerable toxicity, death, withdrawal of consent, or physician decision. Response was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter. The primary end point was ORR per RECIST v1.1 by investigator review. Median age was 55.5 years; 53.8% were male; 53.8% had an ECOG PS of 1; all had received prior chemotherapy. As of the February 17, 2016, data cutoff date, median follow-up duration was 60.9 weeks (range, 11.7-94.0) and 22 (84.6%) patients had discontinued pembrolizumab. Treatment-related AEs occurred in 19 (73.1%) patients, most commonly fatigue and rash (n=6 each, 23.1%). Four (15.4%) patients experienced grade 3-4 treatment-related AEs (lymphopenia, type 2 diabetes mellitus, arthritis, and syncope). No patients died or discontinued pembrolizumab because of a treatment-related AE. There was 1 partial response (n=25; ORR, 4.0% 95% CI, 0.1-20.4); an additional 12 (48.0%) patients experienced stable disease (SD). Median duration of SD was 39.4 weeks (range, 7.1+-85.9+). Median PFS was 2.8 months (95% CI, 1.9-9.1); median OS was 14.4 months (95% CI, 10.3-not reached). Treatment with pembrolizumab monotherapy was associated with a manageable safety profile, and consistent with that of other PD-1 agents, promising antitumor activity in patients with recurrent GBM.