This therapy is a brain-penetrating agent used in various combinations in patients with advanced glioblastoma.
Debiopharm – a company focused on future standards of cancer treatment and infectious diseases – has announced the initiation of an open-label Phase 1/2 study of candidate Debio 0123.
This therapy is a brain-penetrating, selective WEE1 inhibitor used in combination with temozolomide (TMZ) in patients with relapsed or advanced glioblastoma (GBM). It is also being studied in combination with TMZ/RT (SOC) in newly diagnosed patients. The initiation phase of clinical studies is intended to establish a recommended Phase 2 dose of treatment.
Ultimately, Debiopharm aims to meet the pressing need for new therapeutic interventions to improve the quality of life and clinical outcomes of patients living with GBM.
In cancer cells, genomic instability often upregulates DNA damage response (DDR) pathways, increasing the likelihood of resistance to DNA-damaging treatments. Blocking DNA repair pathways through inhibition of essential kinases such as WEE1 may increase cancer vulnerability to standard therapies.
However, preclinical data demonstrate that Debio 0123 successfully crosses the blood-brain barrier and inhibits tumor growth. On the other hand, the combination of Debio 0123 and TMZ has been shown to significantly enhance anti-tumor activity.
Dr. Victor Rodriguez-Freixinos, Associate Medical Director of Oncology at Debiopharm, was optimistic about the results: “The combination of Debio 0123 and temozolomide is promising. The increased replication stress during S phase makes it more dependent on the proper functioning of the G2-M checkpoint.”
He added, “Debio 0123, which acts at both the S-phase and G2-M checkpoints, may make GBM cells more vulnerable to DNA-damaging agents such as temozolomide.”
“The blood-brain barrier, due to its physiological and structural properties, presents a unique challenge for drug delivery and a major obstacle to patient care,” said Dr. Patrick Roth, Zurich University Hospital. Brain penetration is an important source of hope.” For patients suffering from brain tumors. ”
GBM is a highly aggressive tumor of the central nervous system and a leading cause of morbidity and mortality worldwide.
