CTIM-22. PHASE I STUDY RESULTS OF THE ANTIBODY-CYTOKINE FUSION PROTEIN L19TNF IN COMBINATION WITH LOMUSTINE FOR PATIENTS WITH RECURRENT GLIOBLASTOMA REVEAL PROMISING SAFETY AND DURABLE TUMOR RESPONSES

Abstract

Abstract Treatment options for recurrent glioblastoma are limited and there is a need for novel effective therapies. Recently, we showed synergistic preclinical anti-tumor activity of the immunocytokine L19TNF in combination with lomustine in orthotopic immunocompetent glioma mouse models. L19TNF is an antibody-cytokine fusion protein, comprising the pro-inflammatory cytokine tumor necrosis factor (TNF) fused to the antibody L19 that binds to a tumor-specific epitope of the extracellular matrix protein fibronectin. This allows a targeted delivery of therapeutically relevant doses of TNF to the tumor site through intravenous administration while sparing healthy tissues. Here, we present results of the completed phase I part of a phase I/II open label, multicenter, randomized study to investigate L19TNF in combination with lomustine for patients with recurrent glioblastoma (NCT04573192). Fifteen patients were enrolled from February 2021 – January 2023 and treated at three different dose levels of L19TNF in combination with lomustine. Overall, the treatment was well tolerated. The most common adverse events were asymptomatic increase of liver function tests and a decrease of white blood cells and platelets. Serial MRI assessments revealed near-complete responses in 3 patients (20%) and stable disease in 8 (53%) patients. The median progression-free survival was 4.2 months, progression-free survival rate at 6 months was 46% (7/15 patients), and median overall survival has not been reached after a median follow-up of 11 months. Serial blood assessments demonstrated a treatment-associated increase in C-reactive protein, a peripheral marker for inflammation, which correlated with progression-free survival. A patient, who showed a near-complete response that lasted 12 months relapsed at a different location. Subsequent re-challenge with L19TNF and lomustine again led to a partial response. These encouraging results justify further investigations within the phase II part of the clinical trial that is recruiting patients in four countries.