On May 24, 2023 Philogen S.p.A. (BIT:PHIL), a clinical-stage biotech company focused on the development of innovative medicines based on tumor-targeting antibody and small molecule ligands, reported the publication of the latest results of Fibromun (L19TNF, Onfekafusp alfa) in combination with lomustine (an alkylating agent) for the treatment of glioblastoma in Science Translational Medicine describing how the combination treatment cured orthotopic glioma-bearing mice and mediated durable objective responses and major tumor shrinkage in patients with recurrent glioblastoma (Press release, Philogen, MAY 24, 2023, https://www.philogen.com/2023/05/26/philogen-publishes-new-data-on-a-fibromun-based-treatment-combination-in-science-translational-medicine-in-collaboration-with-the-university-hospital-zurich/ [SID1234632147]). The paper can be accessed at the following link.
The study demonstrated that the combination Fibromun and lomustine was highly synergistic and relied on an intact immune system. A thorough investigation of the treatment’s mechanism of action showed that it could transform tumors from being "invisible" to the immune system ("cold") into being easily recognized and attacked ("hot"). This transformation was proven by several indicators: the activation of the tumor endothelium, enhanced tumor DNA damage signaling pathways, treatment-associated tumor necrosis, increased immunogenicity of cancer cells and elevation of immune cell infiltration within the neoplastic mass.
Prof. Michael Weller and Dr. Tobias Weiss of University Hospital Zürich, commented: "We are excited to release this follow-up work based on the Science Translational Medicine paper published together with Philogen back in 2020. The preclinical anti-tumor activity of the combination of Fibromun with lomustine chemotherapy is very promising and the emerging clinical results of the ongoing Phase I/II trial NCT04573192 provide hope for better therapeutic opportunities for patients affected by this serious disease. We now look forward to exploring this promising approach in the Phase II randomized part which is currently starting."
Prof. Dario Neri, co-founder, CEO and CSO of Philogen, commented: "These latest findings show the promising potential of Fibromun for the treatment of glioblastoma, one of the biggest unmet medical needs. While the Phase II randomized part of the GLIOSTAR clinical trial is about to start, the preliminary evidence collected in the Phase I part demonstrates encouraging, durable objective responses in an indication where responses are very rare. We are committed to advancing our research and development efforts, with the ultimate goal of delivering this innovative treatment to patients in need." * * *
About L19TNF (also known as Fibromun)
L19TNF is a fully-human immunomodulatory product consisting of the L19 antibody and tumor necrosis factor (TNF), a strong proinflammatory cytokine. The L19 antibody is specific to the EDB domain of fibronectin and mediates selective localization of TNF to the site of disease while sparing healthy organs. The product is currently investigated in multiple clinical trials for the treatment of soft tissue sarcoma and glioblastoma, both in Europe and in the United States.
Glioblastoma is the most common and most aggressive primary brain tumor. It affects approximately 5 out of 100’000 people every year (Source: Orphanet). Newly diagnosed patients are typically treated with surgery, radiation and temozolomide (chemotherapy), which result in a median Overall Survival (mOS) in the range of 15 months. Virtually all patients progress and may subsequently receive another systemic or local second-line therapy. The mOS of patients at first progression ranges between 4.7 and 9.8 months in previous clinical trials.
About clinical trial NCT04573192
The Phase I/II clinical trial NCT04573192, which investigates the combination of L19TNF and lomustine for the treatment of patients suffering from glioblastoma at first progression after standard of care radiotherapy and chemotherapy. The Phase I part of the trial with escalating dose levels of L19TNF and lomustine is followed by a randomized Phase II part to investigate the efficacy of the combination treatment compared to standard of care lomustine as monotherapy with overall survival as primary endpoint. The first cohort of the phase I part of the study, comprising 6 patients, is presented in this publication.