CTIM-22. THE COMBINATION OF LOMUSTINE AND THE IMMUNOCYTOKINE L19TNF IS A PROMISING TREATMENT FOR RECURRENT GLIOBLASTOMA

Abstract Glioblastoma is the most aggressive primary brain tumor and adults poorly immunogenic. Treatment options for recurrent glioblastoma after standard of care chemoradiation are limited Several immunotherapeutic strategies including peptide vaccination immune checkpoint inhibition have so far failed to improve survival except from potentially regorafenib, no other agent has demonstrated superior activity lomustine. Therefore, there an urgent need more effective treatment glioblastoma. Here, we investigate a new combination based on alkylating chemotherapy lomustine tumor-stroma targeting antibody-cytokine fusion protein L19TNF in preclinical glioma models patients with The strong synergistic anti-tumor several immunocompetent orthotopic curing majority tumor-bearing mice, whereas mono- or therapies example anti-PD1 had only anti-glioma activity. Investigations mechanism action revealed that plus led intratumoral necrosis, DNA damage triggered local response increased MHC-I expression, presentation neoepitopes abundance tumor-infiltrating lymphoid cells. In first treated within phase I/II clinical trial (NCT04573192), was well tolerated, durable objective responses disease stabilizations could be observed also unmethylated MGMT promoter.